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Oncology Glossary

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c-ErbB2: see HER2/neu (human epidermal growth factor receptor 2).

C-peptide: a protein fragment produced during the enzymatic cleavage of proinsulin to create insulin. It is secreted by pancreatic beta cells at equimolar concentrations to insulin but has a half-life in the circulation of two to five times longer. As a result of its greater stability in the peripheral circulation, C-peptide has been measured in research studies as a marker of pancreatic beta cell secretory activity.

c-statistic: a measure of how well a model can discriminate between patients who have a given outcome and those who do not. It is the same as the area under the receiver operating characteristic (ROC) curve.

CA 15-3: mucin-like membrane glycoprotein that can be shed from cancer cells and measured radioimmunologically in the serum. Although not specific for breast cancer, CA 15-3 is most commonly used as a serum tumor marker in patients with metastatic breast cancer.

CA IX: also called the tumor-associated antigen MN. A transmembrane protein that has been detected in several human carcinomas. The full-length clone of MN was found to contain a central region with sequence homology to CA, and therefore, the tumor-associated antigen MN was called CA IX. See also carbonic anhydrase (CA).

CA-125 (cancer antigen 125): a protein produced by the fallopian tubes, the endometrium, and the lining of the abdominal cavity (peritoneum). CA-125 is a tumor marker present in higher than normal amounts in the blood and urine of patients with certain cancers. Typically, women with ovarian cancer have high levels of CA-125. Other conditions associated with elevated levels of CA-125 include endometriosis, pancreatitis, pregnancy, normal menstruation, and pelvic inflammatory disease. CA-125 levels may be used to help diagnose ovarian cancer and to determine whether these tumors are responding to therapy. The normal range for CA-125 is less than 35 U/mL and less than 20 U/mL for women who have been treated for ovarian cancer. Women with ovarian cancer may show values higher than 65 U/mL.

cadherin-11: belongs to the cell adhesion type II cadherin family. Expression of cadherin-11 is increased during the epithelial-to-mesenchymal transition.

cadherins: a family of adhesion molecules that are important in cell-cell homotypic adhesion. Interactions of cadherins with cytoskeletal components result in changes in cell motility, migration, and proliferation. Cadherins exist in several subclasses, including E-cadherins, P-cadherins, and N-cadherins.

calcitonin: a hormone involved in calcium and phosphorus metabolism.

calibration: agreement of predicted risks with observed outcomes, for example, mortality rates.

Cancer of the Prostate Risk Assessment (CAPRA) score: a 0 to 10 score based on a multivariable Cox model that predicts biochemical and clinical (metastasis and mortality) end points after primary treatment for prostate cancer. A postsurgical version (CAPRA-S) offers improved prediction of the same end points after radical prostatectomy.

cancer stem–like cells: a cancer cell that has the potential to transfer disease or to form tumors after transplantation. Cancer stem–like cells have the potential to self-renew (see self-renewal), forming additional tumorigenic cancer cells of similar phenotype, and to give rise to phenotypically diverse cancer cells with more limited potential.

cancer-testis antigens: proteins expressed on the surface of cancer and testicular cells capable of eliciting an immune response outside of the immunologically shielded testis.

canonical pathway: a core pathway established for a given molecule in the cell in which molecular interactions occur in a linear and stepwise manner. Although clustering expression data groups functionally related genes, these groups do not order pathway components according to physical or regulatory relationships. Software is now available for linking significant genes in experiments with a world collection of biologic networks created from millions of individually modeled relationships between genes, proteins, complexes, cells, and tissues. The software allows a view of a study's data integrated in biologic networks according to different biologic context and identifies canonical and noncanonical pathways that connect molecules within a biologic network.

capillary gel electrophoresis: a method for separating biopolymers (eg, DNA and polypeptides) in a capillary filled with a network of cross-linked or entangled linear polymers (sieving matrix) with an applied electric field.

carbogen breathing with nicotinamide: a combination of drug and gas therapy that produces vasodilation and enhanced oxygenation of tumors.

carbonic anhydrase (CA): involved in several physiologic processes, including pH regulation, CO2 and HCO3 transport, and water and electrolyte balance. Eight distinct CA isozymes and additional CA-related proteins have been identified.

carcinoembryonic antigen (CEA): a protein that is used as a tumor marker, especially for GI tumors. After therapy, an increased level of carcinoembryonic antigen in blood is predictive of cancer recurrence. For adult nonsmokers, the normal range is < 2.5 ng/mL; and for smokers the normal range is < 5.0 ng/mL.

carcinoma-specific survival: survival period spanning the time from surgery to death resulting from cancer.

carrier line: the paternal or maternal side of a family that harbors an inherited mutation.

caspase 3 cleavage: an indicator of the activation of caspase 3 during apoptosis. The cleavage is thereby used in assays to define the apoptotic index in a manner that is as specific as TUNEL. See caspases.

caspase 9: mitochondrial release of cytochrome C and the activation of caspase 9 trigger cancer cell death by activating an apoptotic cascade.

caspases: enzymes that belong to a family of cysteine proteases. Caspases are the principal effectors of apoptosis in cells destined for programmed cell death. In the process, initiator caspases activate effector caspases. The processing of proinflammatory cytokines are also carried out by caspases.

castration resistant prostate cancer (CRPC): prostate cancer that progresses despite treatment with androgen-lowering agents that render the patient's serum testosterone to castrate levels.

categorical variables: in statistics, a variable that can take on one of a limited, and usually fixed, number of possible values.

cathepsin: proteins belonging to the papain family. Two members, cathepsin L1 and cathepsin L2, are cysteine proteinase enzymes, which may function in protein turnover, antigen presentation, and bone remodeling.

CBFβ-MYH11: a chromosomal rearrangement seen in acute myeloid leukemia that results in the expression of a chimeric protein, a transcriptional repressor. The inv(16) rearrangement produces a fusion gene, CBFβ/MYH11, which causes a juxtaposition of bands 16q22 (containing the CBFβ gene) and 16p13 (containing the MYH11 gene).

CBP (CREB-binding protein): a coactivator of transcription that binds to phosphorylated CREB, a transcription factor, and assists in CREB-mediated transcription.

CCI-779: also called temsirolimus. See temsirolimus.

CCND1: gene encoding cyclin D1. See cyclin D.

CCND2: gene coding for cyclin D2. See cyclin D.

CCND3: gene coding for cyclin D3. See cyclin D.

CCR9: a chemokine belonging to the CC class of chemokines. See chemokines.

CD10: initially identified as a common acute lymphoblastic leukemia antigen (and called CALLA). CD10 is a cell surface protein with zinc-binding metalloproteinase activity. It is expressed on the surface of neoplastic (eg, lymphoblastic, Burkitt’s and follicular germinal center leukemias) and normal (eg, early lymphoid progenitors, immature B and germinal B cells, T-cell precursors, and neutrophils) cells.

CD105: also known as endoglin. CD105 is selectively expressed on endothelial cells, a subset of bone marrow cells, and activated macrophages.

CD11b/CD18: forms part of the integrin family of adhesion proteins and is present on the surface of neutrophils, macrophages, and lymphocytes. The CD11/CD18 complexes are transmembrane complexes formed from three different CD11 alpha chains and a common CD18 beta chain (eg, CD11a/CD18, CD11b/CD18, CD11c/CD18).

CD11c: a leukocyte integrin that is highly expressed on monocyte-derived dendritic cells.

CD133: encoded by the prominin-1 gene and used as a marker for stem cells of normal tissues tissues (such as neural and hematopoietic stem cells) as well as for tumor stem–like cells of distinct origin (such as brain tumors and breast and colon cancer).

CD138 microbeads: magnetic particles coupled to CD138 monoclonal antibody and used for the positive selection of plasma cells from peripheral blood, bone marrow, and leukapheresis collections of patients with malignant plasma cell diseases. CD138 (also called syndecan 1) is expressed on normal and malignant plasma cells but not on virgin/naive B cells, memory B cells, T cells, or monocytes. CD138 microbeads are also used for the depletion of CD138+ cells.

CD14: receptor for a lipopolysaccharide- and lipopolysaccharide-binding protein that is present on myelomonocytic cells.

CD14+ cells: a marker of monocytes. CD14+ nonproliferating monocytic precursors could be used to generate dendritic cells.

CD16: a component of the low-affinity Fc receptor involved in phagocytosis and antibody-dependent cellular cytotoxicity. CD16 is found on neutrophils, natural killer cells, and macrophages.

CD163: hemoglobin/haptoglobin complex scavenger receptor, expressed almost exclusively on circulating monocytes and tissue macrophages. CD153 is predominantly associated with M2 macrophages.

CD19: found on B cells. CD19 complexes with CD21 and CD81 and acts as a co-receptor for the B-cell receptor leading to B-cell activation and differentiation.

CD1a: a spliced variant of the CD1 gene that is present on epidermal Langerhans cells in skin and some B-cell malignancies.

CD1a+: cell-surface antigen that acts as a marker for dendritic or Langerhans cells.

CD2: cell-surface marker on thymocytes, T cells, and natural killer cells that is involved in T-cell activation.

CD20: cell-surface antigen present on lymphoid B cells. CD20 is a widely used phenotypic marker for typing malignant lymphomas. It is involved in B-cell activation.

CD23: cell-surface receptor present on follicular mantle B cells, activated macrophages, eosinophils, and platelets. CD23 functions as a low-affinity receptor for immunoglobulin E.

CD25: a transmembrane protein present on activated T and B cells. CD25 is the ƒna chain of the interleukin-2 receptor, which associates with the receptor b and g chain to form the high-affinity interleukin-2 receptor complex.

CD27: binds a tumor necrosis factor–like ligand (CD70) and is present on medullary thomocytes and T cells.

CD27+CD45RA+: phenotype of naïve T cells that show the presence of cell surface antigens CD27 and the alternately spliced variant of CD45, CD45RA.

CD27CD45RA+ cells: a population of activated T cells that are effector cells.

CD28: activating receptor for B7 molecules (B7.1 and B7.2) present on naïve T cells. Interaction of CD28 with B7 molecules provides the costimulatory or second signal for T-cell activation.

CD3: a component of the T-cell receptor complex. CD3 is a surface marker specific to T cells and, hence, used to characterize T cells.

CD30: a type I transmembrane protein present on activated T and B cells that may play a role in cell activation and/or differentiation. CD30 is a target for the agent brentuximab vedotin.

CD31: expressed on hematopoietic stem cells. CD31 is also expressed on endothelial cells and belongs to the immunoglobulin superfamily. It mediates adhesion between cells (platelets, monocytes, polymorphonuclear cells, endothelial cells, and discrete populations of circulating lymphocytes) that express CD31. It is an adhesion receptor molecule, responsible for transmitting signals through the adhesion cascade, which involves the integrin family of proteins.

CD34: an antigen selectively expressed on human lymphoid and myeloid hematopoietic progenitor cells. CD34 is also expressed on vascular endothelium.

CD36: a major glycoprotein found on monocytes, macrophages, and some endothelial cells. CD36 plays a major role in cell adhesion and phagocytosis. Also called CD36 antigen, its names include fatty acid translocase, collagen type 1 receptor, and thrombospondin receptor.

CD38: present on macrophages, dendritic cells, and activated B and natural killer cells. CD38 may mediate the adhesion between lymphocytes and endothelial cells.

CD3+/CD4+ lymphocytes: see CD4+ T cells.

CD3+/CD8+ lymphocytes: see CD8+ T cells.

CD3+/CD8+/CD56+ lymphocytes: phenotype that defines T lymphocytes that exert major histocompatibility complex–unrestricted cytotoxicity, such as lymphokine-activated killer cells.

CD3+/HLA-DR+ lymphocytes: activated T cells in which there is upregulation of human leukocyte antigen (HLA) class II antigens, such as HLA-DR, and which are associated with cellular activation.

CD3ζ: gene coding for the CD3 antigen, zeta polypeptide. See CD3.

CD4: the surface antigen that characterizes CD4+ T lymphocytes. CD4 is associated with the T-cell receptor and major histocompatibility complex, necessary for antigen recognition.

CD4+ T cells: T-helper cells, which are characterized by the presence of the CD4 cell-surface marker. Their primary role is to help in the activation of CD8+ T cells specific for a certain antigen.

CD40: receptor for costimulatory signals for B cells through its binding to the CD40 ligand (CD40L). CD40 is present on B cells, monocytes, and dendritic cells.

CD45: also called leukocyte common antigen. CD45 belongs to the family of leukocyte common antigens found on the surface of the majority of human leukocytes. Multiple CD45 isoforms are found on hematopoietic cells. It shows tyrosine phosphatase activity and augments signaling through the B- and T-cell receptors.

CD45RA: a differentially spliced isoform of CD45 that contains coding sequence of exon 2. CD45RA is found on B cells, naïve T cells, and monocytes. See CD45.

CD45RACD45RO+ cells: the phenotype of activated T cells that have differentiated into memory T cells.

CD45RO: an isoform of CD45 that does not contain the coding sequence of exons A, B, and C. CD45RO is present on subsets of T and B cells, monocytes, and macrophages. See CD45.

CD45RO+ T cells: a memory/activation surface marker glycoprotein commonly expressed by T cells infiltrating into tumors. CD45RO is suggestive of mature memory T cell and is different from CD45RA, which is present on immature T cells. See CD45.

CD4+CD25+ T cells: a subset of T regulatory cells that have anergic and suppressive properties and play an important role in the maintenance of self-tolerance. CD4 and CD25 are markers present on regulatory T cells. CD4 is a co-receptor for major histocompatibility complex class II molecules, whereas CD25 is a chain of the interleukin-2 receptor (IL-2R), which associates with CD122 (IL-2Rb chain) and with CD132 (IL-2Rg chain).

CD4/CD8: ratio of helper and cytotoxic T cells.

CD5: a membrane-associated glycoprotein found on all T cells and at low levels on some B cells. CD5 is associated with the T-cell receptor/CD3 complex in T cells and with the B-cell receptor in B cells.

CD56: also called neural cell adhesion molecule. CD56 is present on natural killer cells, a subset of T cells, myeloid leukemia cells, and some large granular lymphocyte leukemias and is involved in cell adhesion.

CD56+/CD3 lymphocytes: the phenotype that defines regulatory natural killer cells that secrete cytokines.

CD57+ natural killer cells: cells that belong to the innate immune system and are specialized to kill target cells that are either infected with viruses or host cells that have become cancerous. CD56 is a surface marker specific to natural killer cells.

CD68: a marker that is used to determine cells of monocyte/macrophage or dendritic lineage.

CD7: belongs to the immunoglobulin gene superfamily. CD7 is the earliest surface marker expressed on T- and natural killer–cell lineages. It is also expressed on bone marrow-derived T, B, natural killer, and myeloid lineage precursors.

CD8: the surface antigen that characterizes CD8+ T lymphocytes. CD8 is associated with the T-cell receptor and major histocompatibility complex, necessary for antigen recognition.

CD8+ T cell: cytotoxic T cell that is the primary effector cells of the immune system. They are characterized by the presence of the CD8 cell-surface marker.

CD8+ T cells: cytotoxic T cells that are the primary effector cells of the immune system. They are characterized by the presence of the CD8 cell-surface marker.

CD80/CD86: members of the immunoglobulin superfamily and present on mature antigen-presenting cells. CD80 and CD86 molecules share their ligands (CD28 and CTLA-4) on T cells and play a major role as costimulatory molecules in major histocompatibility complex class II–mediated peptide antigen presentation.

CD8β: the β-chain of the CD8 antigen present on a subset of thymocytes and cytotoxic T cells. Along with the α-chain, CD8β is a coreceptor for major histocompatibility complex class I molecules.

CD95+: another name for the death receptor Fas. Hence, these are cells that express the Fas receptor. See Fas.

CDC20: gene coding for the cell division cycle 20 homolog. CDC20 is a WD-repeat protein that may regulate APC-dependent proteolysis of mitotic cyclins. It is required for two microtubule-dependent events in cell division (nuclear movement prior to anaphase and chromosome separation).

CDC25 gene family: includes three homologs: CDC25A, CDC25B, and CDC25C. The encoded proteins are all phosphatases. CDC25A activates cyclin E/Cdk2 complexes, is expressed in late G1 and is essential for G1-S phase transition. CDC25B and CDC25C are present in the G2 phase and are necessary for cells to enter mitosis. Of these, CDC25A and CDC25B are frequently overexpressed in human cancers and experimentally exhibit oncogenic potential.

CDH1: cadherin 1 gene. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers.

Cdk inhibitor p27: see Kip1/p27.

cDNA: DNA synthesized from a mature mRNA template in a reaction catalyzed by the enzyme reverse transcriptase.

cDNA microarray: also known as biochip, DNA chip, or gene array. cDNA microarray technology allows for identification of gene expression levels in a biologic sample. cDNAs or oligonucleotides, each representing a given gene, are immobilized on a small chip or nylon membrane and tagged. They serve as probes that will indicate whether they are expressed in biologic samples of interest. Thus, the simultaneous expression of thousands of genes can be monitored concurrently.

CDP860: developed as a molecule that blocks the activity of the beta subunit of PDGFR-β. CDP860 is molecularly engineered to contain two Fab (antigen-binding fragment of an antibody) fragments that are cross-linked through high molecular weight polyethylene glycol.

CDR: complementary determining region of immunoglobulin receptors that determine specificity. These are variable regions of receptor proteins and are responsible for receptor diversity.

CEA652: an HLA-A24–restricted peptide derived from the carcinoembryonic antigen containing two anchor-motif amino acid residues Y and L with a spacer of six amino acids (TYACFVSNL).

CEBPA gene: the CCAAT/enhancer binding protein alpha (CEBPA) gene, which is located on chromosome 19q13.1. It encodes for a member of the basic leucine zipper (bZIP) transcription factor family coordinating myeloid differentiation and cellular growth arrest. Mutations of CEBPA occur in 8%-19% of patients with cytogenetically normal acute myeloid leukemia (AML). N-terminal frameshift mutation leads to an overexpression of a shorter dominant negative isoform of CEBPA. C-terminal in-frame mutation disrupts homo- and heterodimerization domains and impairs DNA binding. Most patients with AML carry a specific combination of two CEBPA mutations (N- and C- terminal) on separate alleles. These biallelic CEBPA mutations are associated with a favorable prognosis.

cell adhesion molecules: integral transmembrane proteins with cytoplasmic tail acting as an anchor, interacting with cytoskeletal proteins within the cell. The extracellular domains interact with extracellular matrix proteins or with cell adhesion molecules from other cells in a homophilic (interacting with the same molecule) or heterophilic (interacting with a different molecule) manner. They have important roles in tissue remodeling and organogenesis.

cell cycle: an ordered progression of events, from a resting state to DNA synthesis to cell division. The major phases of the cell cycle are G0/G1 (GAP 1), S (synthetic) phase, G2 (GAP 2), and M (mitosis).

cell envelope: a specialized structure that forms in terminally differentiated epithelial cells and provides a barrier against mechanical and chemical stress.

cell growth arrest: inhibiting the cell cycle at one of several stages. See cell cycle.

CENP-A, -E, -F: centromere-associated proteins that are localized in kinetochores and provide functions that are critical for normal chromosome motility during mitosis. Prenylation of these proteins is considered to be important to their function. See prenylation.

centroid: mean expression profile of a group of samples for a given set of genes.

centromere: DNA sequences that are responsible for the segregation of each chromosome into daughter cells during cell division. Centromeres are contained in the heterochromatin in cells. As is the case with heterochromatin, the DNA of centromeres does not code for proteins.

cetuximab: also called Erbitux or C225. Cetuximab is a monoclonal antibody that is designed to target the epidermal growth factor receptor and block its signaling activity by initiating receptor activation.

c-FLIP: cellular FADD-like interleukin 1β–converting enzyme-inhibitory protein involved in cell death. See DISC (death-inducing signaling complex).

c-Fos: see Fos.

Chalkley count: a microvessel density scoring system whereby tissue sections stained for tumor vasculature are processed by an observer or a custom software algorithm. The real or virtual Chalkley graticule is positioned over each of three vascular hot spots, determined at low power. The greatest number of vessels that coincide with the 25 points on the Chalkley graticule (after it is rotated through 360° at 20 objective and 10 eyepiece magnification) is averaged for the three hot spot areas to define the Chalkley score.

chaperones: produced in response to stress stimuli, including heat, oxidizing conditions, and exposure to toxic compounds. Molecular chaperones (also called heat shock proteins) protect cells from stress-induced damage by blocking protein aggregation. They can do this by binding and stabilizing proteins at intermediate stages of folding, assembly, translocation, and degradation. Chaperones discriminate against folded proteins by recognizing the hydrophobic features of unfolded proteins. Chaperones also fulfill physiologic functions at normal temperatures, although their expression is low.

Charlson comorbidity index: a weighted index that takes into account the number and seriousness of 19 comorbid diseases to categorize comorbidity burden. The Charlson comorbidity index has prognostic significance in assessing disease outcomes and health resource use and has been validated in the cancer population.

CHEK2 gene (CHK2 gene; cell cycle checkpoint kinase 2 gene): a tumor suppressor gene. Upon ionizing radiation–induced DNA damage, the CHEK2 gene product is activated by the ataxia telangiectasia mutated (ATM) protein and is, in turn, capable of phosphorylating several protein substrates including CDC25A, CDC25C, p53, and BRCA1, leading to cell cycle arrest, apoptosis, and DNA repair. Carriers of germline mutations involving CHEK2 have increased susceptibility to breast cancer.

C-helix of EGFR: x-ray crystallography studies show that the enzymatic kinase portion of the epidermal growth factor receptor is composed of two lobes: the smaller amino terminal N-lobe and the larger carboxy-terminal C-lobe. The alpha C-helix is a part of the smaller N-lobe. ATP is bound in a deep cleft between the two lobes.

chemokines: cytokines that are responsible for chemotactic responses. Chemokines are heparin-binding proteins, which play a role in a variety of biologic processes, the most important being leukocyte chemotaxis. Their classification as C, CC, CXC, and CX3C is based on the position of cysteine residues that form two disulfide bonds. Typically, chemokines mediate their effects through G protein–coupled seven-transmembrane domain receptors, which belong to four families on the basis of their affinity for a given chemokine–CXCR1 to CXCR5, CCR1 to CCR9, XCR1, and CX3CR1.

CHFR: one of several checkpoint systems that regulate mitosis. The CHFR protein possesses an N-terminal forkhead-associated domain, a central ring finger domain, and a C-terminal cysteine-rich region. CHFR regulates a prophase delay when cells are exposed to agents that disrupt microtubules, such as nocodazole and taxol. Loss of CHFR function may be indicative of cancers that are sensitive to chemotherapy.

chi-square tests: a test derived from the chi-square distribution to compare the goodness of fit of theoretical and observed frequency distributions or to compare nominal data derived from unmatched groups of patients.

Child-Pugh: a set of five independent parameters (first developed by Pugh and later revised by Child) that help in predicting prognostic outcome of patients with liver cirrhosis. The five parameters are albumin, bilirubin, prothrombin time/INR, clinical ascites, and encephalopathy. Although none of these parameters is tumor specific, this scoring systems is used for hepatocellular carcinoma by default. Other more tumor and risk factor–specific scoring systems include the Cancer of the Liver Italian Program (CLIP) for hepatitis C–related hepatocellular carcinoma and Chinese University Prognostic Index (CUPI) for hepatitis B–related hepatocellular carcinoma.

ChIP-Seq: chromatin immunoprecipitation followed by massively parallel sequencing. ChIP-Seq identifies the binding sites of DNA-associated proteins. In cancer genomics, this can be used (for example) to map global DNA binding sites of a transcription factor at a high resolution and determine how these interactions regulate gene expression.

chondrosarcoma: a malignant tumor arising from cartilage tissue.

Chou and Talalay approach: a mathematical method used to analyze and define synergy. This method yields a parameter (the combination index) that describes the nature of the interaction between agents (antagonism, addition, and synergism) in a given combination. This method takes into account the potency (median-effect dose values or agent concentrations at 50% effect [IC50]) and the shape (sigmoidicity) of the dose-effect curve based on the median-effect equation.

chromatin: The organization and dense packaging of DNA in the nucleus of cells. See nucleosome.

chromatin 16 inversion: see CBFβ-MYH11.

chromodomain: a motif present in chromatin-remodeling and histone-modifying complexes. Chromodomains are involved in reading the histone code by binding methylated histone tails.

chromogenic in situ hybridization (CISH): a method to detect gene amplification and chromosomal translocations by hybridizing the complementary strand of a nucleotide probe to the sequence of interest. In contrast to fluorescent in situ hybridization (FISH), the DNA probe is detected using a simple enzymatic peroxidase reaction and visualized using a conventional microscope.

chromosomal translocations: a translocation of genetic material from one chromosome to another. Chromosomal translocations occur during meiosis when chromosomal breaks occur. However, in translocations, fragments of one chromosome rejoin to other chromosomes.

CI-1033: an irreversible tyrosine kinase inhibitor of the Erb family of tyrosine kinase receptors. CI-1033 is nonselective for a specific Erb receptor and inhibits tyrosine kinase activities of all members of the Erb family.

CI-1040: selective oral inhibitor of the MEK isoforms, MEK1 and MEK2. MEK proteins are dual-specificity kinases containing two consensus kinase motifs involved in phosphorylation of serine/threonine and tyrosine residues. CI-1040 and other clinically used MEK inhibitors bind to MEK without perturbing the ATP binding site and inhibit phosphorylation of MEK1/MEK2 with subsequent inhibition of ERK signaling.

CIMP: The CpG island methylator phenotype is characterized by widespread, concordant promoter CpG island methylation resulting in silencing of many tumor suppressor genes. CIMP-high (high degree of CIMP) in colorectal cancer is associated with old age, female sex, proximal colon, BRAF mutation and microsatellite instability, and inversely with chromosomal instability, TP53 mutation, WNT/β-catenin (CTNNB1) activation, and genome-wide DNA hypomethylation.

circulating DNA: cell-free DNA that is present in blood. Circulating DNA can be detected in free form in sera or plasma. Circulating tumor DNA in the blood of patients with cancer can be identical to that of the patients’ tumors. Therefore, circulating DNA has the potential of being a useful surrogate assay for cancer detection.

circulating endothelial cells: probably derived from blood vessel wall turnover and found to be increased in patients with various types of cancer and various other conditions including mechanical, inflammatory, infective, ischaemic and autoimmune states. The presence of circulating endothelial cells has recently been recognized as a useful marker of vascular damage.

circulating tumor cell: demonstration of isolated tumor cell circulation/dissemination in the peripheral blood.

circulating tumor cells: demonstration of isolated tumor cell circulation/dissemination in the peripheral blood.

circumferential resection margin: the least distance between the radial extent of the tumor and the cut surgical resection radial margin.

cisplatin: an inorganic platinum agent (cis-diamminedichloroplatinum) with antineoplastic activity. Cisplatin forms highly reactive, charged, platinum complexes, which bind to nucleophilic groups such as GC-rich sites in DNA, inducing intrastrand and interstrand DNA cross-links as well as DNA-protein cross-links. These cross-links result in apoptosis and cell growth inhibition. Carboplatin and oxaliplatin are other members of this class.

c-Jun: a member of the early response gene family. The c-jun (also designated an oncogene) protein product is a key component of the transcriptional factor, AP-1. Along with its normal partner, fos (a protein product of c-fos), the jun-fos heterodimer acts as a transactivator and plays a key role in regulating gene expression and signal transduction. See AP-1 (activator protein-1).

CK19 (cytokeratin-19): cytokeratin belonging to the intermediate filaments, which create a cytoskeleton in almost all cells. CK19 is normally not expressed in the hematopoietic cells, although it is commonly expressed in epithelial cells such as mammary cells, either normal or neoplastic.

CK20: a low-molecular-weight cytokeratin and a component of the intermediate filament present in the cytoplasm of epithelial cells and its expression is restricted to the small and large intestine and Merkel cells. CK20 is a valuable diagnostic marker that helps to distinguish different types of carcinomas, notably when presenting as metastases, given that CK20 is not expressed in small-cell carcinomas of various sites but is present in most Merkel cell carcinomas.

c-Kit: a tyrosine kinase receptor that dimerizes after ligand binding and is autophosphorylated on intracellular tyrosine residues.

Clark’s level of invasion: the microstage of malignant melanoma is defined by Breslow’s and Clark’s classifications. The Clark classification defines the anatomical level of primary tumor invasion in the skin and is reported as level I (involves only the epidermis and considered as noninvasive/in situ lesions, level II (involves invasion of the papillary dermis, not reaching the papillary-reticular dermal interface), level III (involves complete invasion and expansion into the papillary dermis, not penetrating the reticular dermis), level IV (involves invasion into the reticular dermis, not subcutaneous tissue), and level V (involves invasion into the subcutaneous tissue via the reticular dermis). The revised American Joint Committee on Cancer staging includes Clark?s level of invasion when defining subcategories of T1 melanomas, but it is not used for thicker melanomas (ie, T2-T4).

class prediction algorithms: computer programs used to combine known data on samples to predict unknown characteristics.

classifiers: a mathematical function that assigns a specimen to a class on the basis of the the values of a set of component variables or features. The classes are predefined and often represent diagnostic categories or prognostic categories. Developing a completely specified classifier involves determining which features should be included as components, what mathematical form to use for combining the values of the different features, what values to use for the parameters of the mathematical form, and what cutoff values to use for converting a continuous function into a discrete classification. Some classifiers are based on the level of expression of a single protein or the presence of a specific DNA polymorphism. With gene expression profiling, classifiers may contain dozens of components, representing the level of expression of genes that are selected from tens of thousands of candidate genes. A completely defined classifier will select patients and stratify patients for therapy and needs to be validated independently of the study used to develop it.

clathrin: vesicles coated with clathrin mediate endocytosis of plasma membrane proteins and transport of proteins from the trans-Golgi network to the endosomal/lysosomal system.

CLIA certifification: Clinical Laboratory Improvement Amendments put in place by Congress in 1988 to establish quality standards in laboratory testing.

clinical practice guidelines: statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.

clinical target volume (CTV): the volume of tissue that contains a demonstrable gross tumor volume and/or subclinical malignant disease with a high enough likelihood of containing subclinical (ie, microscopic) malignant disease to warrant treatment with radiation. The clinical tumor volume is an oncologic definition and is thus independent of technical factors.

clonal evolution (of tumor): accumulation of mutations in cancer cells guided by selective forces. The genomic content of cells within a single tumor can be heterogeneous as a result of differences in the mutation history of the lineage of individual cells. A growth (dis)advantage as a result of the mostly random mutations creates selective pressure. Cells with the relatively best genotype eventually dominate in the tumor.

cluster: the unexpectedly high incidence of a particular disease or phenotype (usually caused by a founder mutation) within a defined geographic area.

clustering: organization of data consisting of many variables (multivariate data) into classes with similar patterns. Hierarchical clustering creates a dendrogram on the basis of pairwise similarities in gene expression within a set of samples. Samples within a cluster are more similar to one another than to samples outside the cluster. The vertical length of branches in the tree represents the extent of similarity between the samples. Thus, the shorter the branch length, the fewer the differences between the samples.

c-myc: an oncoprotein. c-myc is a transcriptional factor that activates the transcription of growth-associated genes. Its activity is positively modulated by heterodimerization with Max.

CNF1010: a soluble analog of 17-AAG. See 17-AAG (17-allylaminogeldanamycin).

co-activators: proteins that bind to transcription activators and assist in transcription.

Cockayne syndrome: The CSA and CSB genes encode proteins involved in the repair of transcriptionally active DNA (transcription-coupled repair). Homozygous mutation of one of these genes results in the childhood condition, Cockayne Syndrome, which is characterized by ultraviolet sensitivity, short stature, and the appearance of premature aging. Unlike other DNA repair diseases, Cockayne syndrome does not predispose to cancer.

coding polymorphism: genetic polymorphism that occurs in the coding sequence of a gene. See single nucleotide polymorphism (SNP).

cohort study: a form of longitudinal study in which a group of people are observed over a period of time to evaluate whether exposure to a certain factor (or intervention) impacts their outcomes.

collagen: the principal protein of the skin, tendons, cartilage, bone, and connective tissue.

collagen alpha II type I: codes for type II collagen. Defects in type II collagen are associated with chondrodysplasias, including achondrogenesis II, hypochondrogenesis, spondyloepiphyseal dysplasia congenita, Kniest dysplasia, and Stickler syndrome.

collapsin: belongs to a family of secreted and transmembrane proteins that serve as repulsive signals in axonal and neuronal development.

comorbidity: having two or more diseases at the same time.

comparative effectiveness research: the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of comparative effectiveness research is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at the individual and population levels.

comparative genomic hybridization (CGH): a molecular cytogenetic method of screening tumor samples for genetic changes showing characteristic patterns for copy number changes (mutations cannot be detected by CGH) at chromosomal and subchromosomal levels. Alterations in patterns are classified as DNA gains and losses. The method consists of isolating DNA from tumors and healthy tissues (reference) and labeling each with a different color or fluorophore. The two samples are then mixed and hybridized to normal metaphase chromosomes. In the case of array or matrix CGH, the hybridization mixing is done on a slide with thousands of DNA probes. The detection system is varied but basically determines the color ratio along the chromosomes to determine DNA regions that might be gained or lost in tumor samples.

competing risk regression: a statistical method that accounts for competing risks. Cumulative incidence functions are compared instead of survival functions (Fine J, et al: J Am Stat Assoc 94:496-509, 1999).

competing risks: events that prevent an event of interest from occurring. "Competing risks are said to be present when a patient is at risk of more than one mutually exclusive event, such as death from different causes, and the occurrence of one of these will prevent any other event from ever happening" (Hinchliffe SR: Presented at the University of Leicester, 2012).

complement-dependent lysis (CDC): process of target cell lysis by a cascade of soluble proteins activated by cells coated with immunoglobulin G or immunoglobulin GM antibodies.

complementary and alternative medicine: health care approaches developed outside of mainstream Western, or conventional, medicine for specific conditions or overall well-being.

comprehensive geriatric assessment (CGA): multidimensional, interdisciplinary diagnostic process focusing on determining an older person's medical, psychosocial, and functional capabilities to develop coordinated and integrated plans for treatment and long-term follow-up.

computed tomography (CT) scan: a series of pictures created by a computer linked to an x-ray machine taken of the inside of the body from different angles.

concordance index (c-index): the probability that given two randomly selected patients, the patient with the worst outcome is, in fact, predicted to have the worst outcome. The measure is similar to an area under the receiver operating characteristics curve and ranges from 0.5 (chance or coin flip) to 1.0 (perfect ability to rank patients).

conformal radiation therapy: an irradiation technique developed to limit the highest radiation dose to volumes at risk for tumors while sparing surrounding normal tissues. Treatment planning is based on three-dimensional reconstructions of individual patient anatomy.

confounding variables: extraneous variables in a statistical model that are associated/correlated with both the independent and dependent variables but are not on the causal pathway between independent and dependent variables. When confounding variables are present, crude (unadjusted) statistical models describing the association between independent and dependent variables are biased (ie, wrong) as the risk estimate includes the effect of the confounding variable as well (type 1 error). As a result, to properly describe the relationship between independent and dependent variables, a multivariable model that includes both the independent variable and all relevant confounding variables as predictors must be executed.

consolidation treatment: antineoplastic treatment in patients with cancer with complete remission of malignancy, aimed at the elimination of remaining malignant cells and therefore at preventing relapse.

CONSORT statement: an evidence-based, minimum set of recommendations for reporting randomized trials that offer a standard way for authors to prepare reports of trial findings, facilitating their complete and transparent reporting and aiding their critical appraisal and interpretation.

Contig 51037: contig sequence previously identified in a DNA microarray study of breast cancer recurrence risk.

continual reassessment study designs: study designs that use statistical modeling and are employed in dose-finding clinical trials to estimate the dose at which the desired toxicity level can be expected to minimize the risk of toxicity to patients.

continuous hyperfractionated accelerated radiotherapy (CHART): a technique of delivering radiation dose over a short period of time, 12 days rather than 30 days.

copy number aberration (CNA): defines the net increase or net decrease in gene copy number (ie, gene dosage). It includes extensive low-amplitude and focal high-amplitude changes in gene copy number. Large regional copy number changes—involving chromosomal fragments, chromosomal arms, or whole chromosomes—are typically of low amplitude and commonly referred to as gains and losses. Focal reduction or increment in copy number of a specific gene in the genome without a proportional increase in other—or only few neighboring—genes are commonly denoted as amplification and deletion, respectively. Amplifications can include hundreds of repeat copies of a gene, which may sometimes occur via the excision of a copy of the repeating sequence from the chromosome and its extra chromosomal replication (so-called double minute chromosomes). In a deletion, one or both copies—so-called alleles—of a gene (which are present at an autosomal locus of the normal human genome) can be lost, commonly designated as hemizygous and homozygous deletion, respectively.

copy number alteration: a structural variation in the genome with an increased (amplification) or decreased (deletion) number of copies of a gene or region.

copy number gain/loss: chromosomal amplifications or deletions that result in gains or losses, respectively, of genes in the affected regions of the chromosome. Chromosomal amplification may result in chromosomes acquiring multiple copies of genes. Chromosomal deletions may result in biallelic gene loss when deletions occur in corresponding regions of both chromosomes.

co-regulatory receptors: molecules that transmit additional signals through B-cell and T-cell receptors.

co-repressors: accessory proteins that bind to transcriptional factor repressor domains and recruit other components to the transcriptional machinery.

cost-effectiveness analysis: an economic evaluation in which the costs and consequences of alternative interventions are expressed as a cost per unit of health outcome. Cost-effectiveness analysis is used to determine technical efficiency (ie, comparison of costs and consequences of competing interventions for a given patient group within a given budget).

costimulatory molecules: molecules that transmit additional signals through B-cell and T-cell receptors.

COX (cyclooxygenase): a prostaglandin endoperoxide synthase, COX enzymes are responsible for the production of prostaglandins, intracellular messengers found at high levels at inflammation sites. Of COX-1 and COX-2, the latter has received much attention as a result of drug development that has targeted COX-2 for selectively down regulating inflammatory processes.

Cox proportional hazards: see Cox proportional hazards regression model.

Cox proportional hazards regression: see Cox proportional hazards regression model.

Cox proportional hazards regression model: a statistical model for regression analysis of censored survival data, examining the relationship of censored survival distribution to one or more covariates. This model produces a baseline survival curve, covariate coefficient estimates with their standard errors, risk ratios, 95% CIs, and significance levels.

Cox regression analysis: see Cox proportional hazards regression model.

COX-2: see COX (cyclooxygenase).

COX5A: gene coding for the cytochrome c oxidase subunit Va protein, which shows cytochrome oxidase activity.

CP-675206: a fully human monoclonal antibody with high affinity for CTLA4. Binding of CP-675206 to CTLA4 antagonizes the binding of CTLA4 to B7 ligands, resulting in enhanced T-cell activation and proliferation.

CpG dinucleotides: DNA sequences composed of a cytidine connected to a guanosine through a phosphate residue. CpG dinucleotides are under-represented in mammalian genomes and tend to form clusters in CpG-rich regions (also referred to as CpG islands when they fulfill certain criteria). Cytidines in the context of CpG dinucleotides can be methylated to 5-methylcytidine by DNA methyltransferases and are often associated with transcriptional repression when located in regions that are relevant to regulatory functions.

CpG island: DNA sequences with a high density of CpGs are termed CpG islands. CpG islands are typically unmethylated in normal tissues but often become methylated in tumors. The patterns of hypermethylated CpG islands vary according to the histologic origin of the tumor.

CpG island microarrays: a microarray containing CpG islands (including the CpG islands of promoter regions and the first exon of many transcripted genes) as probes.

c-Raf: see Raf.

Cramer's V statistic: a statistic that provides a quantitative measure of the strength of association between the two variables in a contingency table (which cannot be obtained from the P value). Cramer’s V values range from 0 to 1, with 0 indicating no relationship and 1 indicating perfect association. Traditionally, values between 0.36 and 0.49 indicate a substantial relationship, and values greater than 0.50 indicate a very strong relationship.

CREB (cyclic AMP response element binding protein): a transcription factor whose expression is induced in the presence of cyclic AMP.

CREM: a cAMP response-element modulator protein, which binds to promoter elements of genes that are transcribed in a cAMP-dependent manner. CREM belongs to the CREB (cAMP response element binding protein) family of transcriptional factors and to the bZIP (basic region/leucine zipper) superfamily of proteins characterized by a C-terminal basic domain (mediating DNA binding) and a leucine zipper motif (mediating dimerization).

cross-presentation: a process of antigen-specific T-cell stimulation by dendritic cells and other antigen-presenting cells, which take up exogenous antigen and process it for recognition by HLA class I–restricted cytotoxic T lymphocytes, and in some cases, HLA class II–restricted antigen presentation to CD4T lymphocytes.

cross-priming: the mechanism by which T cells are primed at the site of the tumor. Antigen-presenting cells capture environmental antigens and present them to T cells to stimulate antigen-specific immunity.

cross talk: the process of intercellular receptor activation by another activated receptor. It may also be viewed as cooperation among receptors, whereby activation of one receptor enhances the activity of another receptor in the absence of heterodimerization.

cross validation: a class of methods used for estimating the predictive accuracy of a classifier within the study used to develop the classifier. This process can be seen as a repeated model development and testing on random data partitions. The classifiers must be developed from scratch on each training set with no preselection of component genes using all of the data. These methods estimate the predictive accuracy of the model that can be developed using the full data set. See training set.

CSD melanoma: melanomas with chronic sun-induced damage of the surrounding dermis, as determined by the microscopic presence of marked solar elastosis.

CSF1R (colony stimulating factor 1 receptor): The receptor for colony stimulating factor 1, a cytokine that controls the production, differentiation, and function of macrophages. CSF1R is a transmembrane tyrosine kinase and member of the CSF1/platelet-derived growth factor receptor family. Mutations in the CSF1R gene have been associated with a predisposition to myeloid malignancy.

c-Src: the cellular homolog of v-src (viral-src). c-Src is a nonreceptor tyrosine kinase with pleiotropic activities. Typically activated by growth factor receptors, c-Src mediates the processes of survival and proliferation. It is generally activated in several epithelial tumors.

C-telopeptide cross-links (CTx) of type I collagen: covalent chemical links that connect collagen fibrils. Cross-linking between molecules in fibrils produces a very stable protein structure, which contributes to collagen’s tissue-strengthening function. The common crosslinks of bone resorption markers are pyridinium cross-links, cross-linked N-terminal telopeptides of type I collagen (NTx), and C-terminal telopeptides of type I collagen (CTx) that are found in the circulation and are excreted into the urine. The telopeptides of type I collagen have proven to be more sensitive markers than the pyridinium cross-links.

CTGF (connective-tissue growth factor): a secreted protein belonging to the family of CCN proteins (CTGF, cysteine-rich 61, nephroblastoma overexpressed) with functional domains that mediate interactions with growth factors, integrins, proteoglycans, and extracellular matrix. It is implicated in several cellular events, including angiogenesis, chondrogenesis and formation of connective tissues. Induced by TGF-β/SMAD-dependent pathway, CTGF activates cell signaling, attachment, migration, cytoskeletal reorganization, and extracellular matrix production.

CTLA4 (CD152): receptor on activated T cells that binds B7 molecules with a higher affinity than CD28, downregulating T-cell responses by inhibiting CD28 signaling.

CTSB: gene encoding for cathepsin B, a lysosomal peptidase.

CTSL2 (cathepsin L2): a protein belonging to the papain family. CTSL2 is the gene for a cysteine proteinase enzyme, which may function in protein turnover, antigen presentation, and bone remodeling.

cumulative incidence: a statistical measure of an event of interest (eg, relapse, death, second malignant neoplasm, a specific disease) occurring in a specified period of time in the population at risk. It is calculated using the formula: (number of new cases of the event of interest)/(total population at risk).

cumulative incidence of relapse (CIR): the use of competing risk analyses indicated in the presence of competing events (such as death and relapse); the Gray’s test is a recommended method to estimate cumulative incidence of relapse.

cumulative risk: a measure of risk of an event (usually disease occurrence) during a specified time period.

cutaneous B-cell lymphoma (CBCL): B-cell non-Hodgkin lymphomas with only skin lesions at the time of diagnosis. This heterogeneous group includes primary cutaneous marginal zone lymphoma, primarily follicle center lymphoma (CBCL with an indolent clinical behavior) and primary cutaneous large B-cell lymphoma, leg type (CBCL with an intermediate clinical behavior).

CX3CR1: gene coding for the chemokine receptor (C-X3-C), which is a member of the rhodopsin family of G-protein coupled receptors and perhaps a receptor for a chemokine peptide ligand.

CXCR4: gene encoding chemokine (C-X-C motif) receptor 4, which is a G-protein–coupled receptor for the chemokine stromal cell–derived factor-1. CXCR4 signaling activates Ras and PI3 kinase pathways and induces the transcription factors AP-1 and chemokine-regulated genes.

CYBA: gene encoding for the alpha subunit of cytochrome b558, a component of NAD(P)H oxidase. It is suggested that CYBA may play a role in production of reactive oxygen species in endothelial cells.

cyclin A: the positive regulatory subunit of the CDK2-cyclin A complex, active during the S phase of the cell cycle. Each phase of the cell cycle is characterized by different cyclin-dependent kinases and cyclin complexes.

cyclin B1: gene coding for cyclin B1, which is required for the activation of mitosis (or maturation) promoting factor. Cyclin B1 expression varies in the cell cycle, is minimally expressed in G1, begins to rise in S phase, and peaks at the G2/M transition.

cyclin D: a protein that is present at high levels when resting cells enter a state of active division. Cyclin D acts in the G1 phase of the cell cycle. Cyclins are typically paired with cyclin-dependent kinases (CDK) that need to be activated for cell cycle to proceed. Cyclin D pairs with CDK4 and CDK6 and acts in the G1 phase of the cell cycle.

cyclin D2: a member of the family of cyclin D. See cyclin D.

cyclin-dependent kinase 4 (CDK4): a member of the serine/threonine protein kinase family. CDK4 is the catalytic subunit of the kinase complex (cyclin D/CDK4) important in the G1 phase of the cell cycle. Regulatory subunits of this complex are Cyclin D (positive) and CDK inhibitors. Alternately spliced forms of CDK4 are known and some phosphorylation targets (eg, Rb) are also known to modulate events that are necessary for cell-cycle progression. See cyclin D.

cyclin E: a positive regulator of cyclin-dependent kinase 2 (CDK2). Cyclin E is a G1 cyclin expressed in the G1 phase of the cell cycle with its peak activity seen at the G1/S boundary of the cell cycle. Its expression is downregulated in the S phase of growth; however, it is a critical molecule that dictates cell entry into the S phase and is considered the master regulator for S-phase entry.

cyclodextrins: a family of compounds (sometimes called cycloamyloses) made up of sugar molecules bound together in a ring (cyclic oligosaccharides).

CYP2D6: an isozyme of the cytochrome P450 mixed-function oxidase system involved in the metabolism of xenobiotics including drugs. Several clinical important drugs are substrates for CYP2D6 including ß-blocker, antiarrhythmics and antidepressant drugs, codeine, and tamoxifen.

CYP3A4: gene encoding cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4. Notably present in the liver, the mixed-function oxidase is the most important enzyme involved in the metabolism of xenobiotics and oxidizes a wide range of substrates, including taxanes.

cytochrome P450: a family of mixed-function oxidase enzymes that are involved in the oxidative metabolism of endogenous substances and xenobiotics. Several isoforms of cytochrome P450 exist with specificity for a given class of drugs, which are metabolized via the system. In addition, several classes of drugs have been shown to induce and/or inhibit cytochrome P450. This interaction may have important consequences for the pharmacokinetics of numerous drugs and may serve as a mechanism for drug-drug interactions.

cytochrome c: a protein present in mitochondrial membranes. It is important in the energy generation machinery of the cell. In addition, when cells are damaged as a result of apoptosis, the release of cytochrome c is a part of the cascade of reactions leading to programmed cell death.

cytochrome P450 c17 (CYP17): a critical enzyme in testosterone synthesis with 17α-hydroxylase and c17, 20 lyase activities, which are necessary for the conversion of pregnenolone to 17α-hydroxypregnenolone and dehydroepiandrosterone and for the conversion of progesterone to 17α-hydroxyprogesterone, respectively.

cytofluorimetric dimer assay: an indirect cytofluorimetric assay, which allows the recognition of T cells with peptide-specific T-cell receptor. These cells are recognized because of their ability to bind the target cognate peptide, which is previously conjugated to a chimeric dimeric molecule composed by the Fc portion of a mouse immunoglobulin and the binding site of HLA-A(*)02.01 molecules.

cytogenetic-morphologic correlations: studies that correlate cytogenetic findings in tumor cells to tumor morphology. Cytogenetically, the structure of the chromosome is analyzed for chromosomal aberrations using cytogenetics such as fluorescent in situ hybridization and comparative genomic hybridization. Tumor morphology is typically determined by a clinical pathologist using histochemical techniques.

cytogenetically normal acute myeloid leukemia (AML): acute myeloid leukemia with a normal karyotype at diagnosis on the basis of the microscopic analysis of ≥ 20 metaphase cells in bone marrow specimens subjected to short-term cultures; approximately 45% of patients with acute myeloid leukemia are cytogenetically normal.

cytokeratins: members of a large family of intermediate filament cytoskeletal proteins. Intermediate filament proteins are expressed in a tissue-specific manner and are assembled as filamentous arrays. Intermediate filament proteins have diverse biologic functions and their association with a wide array of human diseases resulting from aberrant post-translational modifications, limited proteolysis, and cross linking.

cytokines: cell communication molecules that are secreted in response to external stimuli.

cytopathic effect (CPE): damage to cells resulting from viral infection. Viruses can target cells and cause cell death. A CPE assay can be used to determine the titer of viral stocks.

cytotoxic T lymphocyte: a T lymphocyte (a type of white blood cell) that is capable of inducing the death of tumor cells; they also kill cells that are infected with viruses.

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