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Oncology Glossary

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β-actin: a protein that is ubiquitous to all eukaryotic cells, used as a reference for other differentially expressed proteins. See ACTB.

β-catenin: originally identified as a component of cell-cell adhesion complexes composed of cadherins and actin. β-catenin has now been shown to be a downstream signaling molecule in the Wnt signaling pathway.

β-hCG (beta human chorionic gonadotropin): the beta subunit of the human chorionic gonadotropin.

B7: family of cell surface proteins that function as costimulatory molecules transducing second signals for T-cell–dependent immune responses.

B7.1 (CD80): ligand for CD28 and CTLA4, belonging to the immunoglobulin superfamily. B7.1 is present on antigen-presenting cells. In its interaction with CD28, it is a costimulator for T-cell activation. Its interaction with CTLA4 occurs with a higher affinity than its interaction with CD28, leading to inhibition of CD28 signaling.

B7.2 (CD86): ligand for CD28 and CTLA4, belonging to the immunoglobulin superfamily. B7.2 is present on antigen-presenting cells. In its interaction with CD28, it is a costimulator for T-cell activation. Its interaction with CTLA4 occurs with a higher affinity than its interaction with CD28, leading to inhibition of CD28 signaling.

BAALC (brain and acute leukemia, cytoplasmic): gene located on chromosome 8q22.3 that encodes a protein with no homology to any known proteins or functional domains. Expression of this gene is found primarily in neuroectoderm-derived tissues and hematopoietic precursors.

BAC clones: derived from a cloning system designed to clone DNA fragments in excess of 100 to 300 kb. F-factor-based bacterial artificial chromosome (BAC) clones are a library of genomic DNA fragments that are plasmid based and easy to isolate, making them feasible for genomic analysis.

BAD: a proapoptotic member of the Bcl-2 family of proteins, BAD’S phosphorylation leads to its inability to interact with and inhibit proteins that are involved in cell survival pathways.

BAG1: gene encoding Bcl-2–associated athanogene. By binding to Bcl-2 it enhances the antiapoptotic effects of Bcl-2 and is a link between growth factor receptors and antiapoptotic mechanisms. Alternate translation initiation sites are responsible for the expression of at least three protein isoforms that may have different functions.

BAGE: also called B melanoma antigen 1 precursor. The gene family codes for tumor-associated antigens that are presented by human leukocyte antigen class I molecules and recognized by CD8 cytolytic T lymphocytes.

Bak: a proapoptotic protein belonging to the Bcl-2 family of proteins.

Barrett's metaplasia/Barrett's mucosa: a condition in which stratified squamous cells of the esophagus are replaced by specialized columnar epithelial cells similar to ones found in the intestine. Barrett's metaplasia, generally developing in patients suffering from gastroesophageal reflux disease, is a predisposing condition that increases the risk of developing esophageal adenocarcinoma.

Barrett’s mucosa/Barrett's metaplasia: a condition in which stratified squamous cells of the esophagus are replaced by specialized columnar epithelial cells similar to ones found in the intestine. Barrett's metaplasia, generally developing in patients suffering from gastroesophageal reflux disease, is a predisposing condition that increases the risk of developing esophageal adenocarcinoma.

basal breast cancer: breast tumors characterized by gene expression signature similar to that of the basal/myoepithelial cells of the breast and reported to have transcriptomic characteristics similar to those of tumors arising in BRCA1 germline mutation carriers. Basal breast cancer has been associated with aggressive behavior and poor prognosis.

basal-like: a gene expression pattern displayed by a subset of breast cancers (approximately 15%-20%), usually in the setting of a triple-negative phenotype, with increased expression of a variety of cytokeratins and other markers such as epidermal growth factor receptor typically found in the basilar epithelium of the breast.

base excision repair (BER): one of the major DNA repair pathways that repairs simple DNA base lesions, such as the products of deamination, oxidation, and alkylation. In BER, a damaged base is removed by a DNA glycosylase, followed by excision of the resulting sugar phosphate. The small gap left in the DNA helix is then filled in by the sequential action of DNA polymerase and DNA ligase.

basket trial: a trial that investigates the effects of targeted agents against specific molecular aberrations across multiple histologic subtypes at the same time.

Bax: has proapoptotic functions and belongs to the Bcl-2 family of proteins. As a result of its extensive sequence homology with Bcl-2, Bax can form heterodimers with Bcl-2. Homo- or heterodimers of Bax repress the antiapoptotic activity of Bcl-2. See Bcl-2.

BAY 43-9006: also called sorafenib. BAY 43-9006 is an inhibitor with inhibitory activities on Raf kinase and vascular epithelial growth factor receptor.

Bayesian statistics: alternative statistical methods that incorporate prior knowledge into the probability calculations, adjusting for accumulated experience. Trials using Bayesian statistics can provide faster, more useful clinical trial information under certain circumstances than traditional statistical methods.

BBC3 (Bcl-2 binding component 3): depending on splicing, several variants of this gene are expressed. The protein is exclusively mitochondrial and binds to Bcl-2 and Bcl-XL through a BH3 domain. Involved in caspase activation and release of cytochrome c from the mitochondria, it is a negative regular of cell growth. The gene is also known as JFY1, PUMA (p53-upregulated modulator of apoptosis), or PUMA/JFY1.

Bcl-2: first discovered as a translocated locus [t(14;22)] in B-cell leukemias. Bcl-2 is an antiapoptotic protein that protects cells from programmed cell death by preventing the activation of proapoptotic caspase proteins.

BCL2: gene that codes for the Bcl-2 protein. See Bcl-2.

Bcl-6: the B-cell lymphoma-6 transcriptional repressor, containing conserved repressor and zinc finger motifs. Bcl-6 acts by recruiting co-repressor proteins.

Bcl-6 inhibitor peptides: peptides engineered to inhibit the interface between Bcl-6 and its co-repressor partner.

BCL7a (B-cell CLL/lymphoma 7a): gene identified from a three-way translocation t(8;14;12)(q24.1;q32.3;q24.1), which also involved myc and immunoglobulin H, in a Burkitt’s lymphoma cell line. The protein coded by this gene (BCL-7A) exhibits no recognizable protein motifs but shows homology with the actin-binding protein caldesmon.

Bcl-X: an antiapoptotic member of the Bcl-2 family of proteins. Bcl-X is a homolog of Bcl-2. Depending on splicing, Bcl-X may be present either as the short (Bcl-XS) or the long (Bcl-XL) form. Of these, Bcl-XL has antiapoptotic properties similar to Bcl-2.

BCoR: a co-repressor that interacts with Bcl-6.

BCR: B-cell antigen receptor that is a prerequisite for antigen recognition by B cells and for generation of a specific antibody immune response. BCR signaling is involved in the pathogenesis of several B-cell malignancies.

BCR-ABL: a hallmark feature of patients with chronic myelogenous leukemia. The fusion of BCR-ABL results from a genetic translocation [t(9;22)] between chromosome 9 (the locus for Abl) and 22 (the locus for BCR), resulting in the Philadelphia chromosome. The BCR-ABL gene product has constitutive tyrosine kinase activity that is responsible for unfettered proliferation.

beta-catenin: originally identified as a component of cell-cell adhesion complexes composed of cadherins and actin. β-catenin has now been shown to be a downstream signaling molecule in the Wnt signaling pathway.

bevacizumab: also called Avastin (Genentech, South San Francisco, CA). Bevacizumab is a recombinant, humanized, monoclonal antibody that binds and neutralizes the vascular endothelial growth factor, thus acting as an antiangiogenic agent.

bFGF (fibroblast growth factor 2 [basic]): the prototype of the fibroblast growth factor family, which currently has up to 18 members of structurally related proteins. It acts as a mitogen or proliferative signal for several cell types, including fibroblasts, smooth muscle cells, and endothelial cells and is also involved in the angiogenic process and in the formation of mesenchyme.

BH3-binding domain: hydrophobic groove present in Bcl-2, and some related proteins, that acts as a binding target for the BH3 domain of other proteins. The BH3-binding domain is the primary target for certain small molecule inhibitor drugs that prevent BH3-domain binding and induce apoptosis.

BH3 (Bcl-2 homology 3) domain: proteins with BH3 domains are proapoptotic in nature and mediate cell death in response to specific stimuli.

bHLH (basic helix-loop-helix) proteins: transcription factors that play critical roles in biologic pathways ( such as cell lineage determination, proliferation, and differentiation). They are involved in various differentiation processes such as skeletal myogenesis, neurogenesis, and hematopoiesis. Possessing highly basic regions and helix-loop-helix motifs (as determined by x-ray crystallography), bHLH proteins form homo- or heterodimers (with other bHLH proteins) through their helix-loop-helix domains, which enable their basic regions to form DNA-binding motifs that recognize specific sequences called E-box sequences. They can act as transcription activators as well as repressors.

biallelic: the condition in which both alleles of a gene are mutated.

Bid: see Bid (BH3-interacting domain death agonist).

Bid (BH3-interacting domain death agonist): a member of the Bcl-2 family of proteins, Bid is proapoptotic. After induction of apoptosis, Bid, which usually resides in the cytoplasm, translocates to the mitochondria. The translocation of Bid occurs as a consequence of its truncation (tBid) by caspase-8 and its subsequent myristoylation. tBid selectively binds to the outer mitochondrial membrane, where it is responsible for the release of cytochrome c, a molecule that amplifies the apoptotic cascade.

biochemical failure: an increase in prostate-specific antigen after prostate cancer treatment that meets the criteria for progression, such as three consecutive increases after radiotherapy (American Society for Radiation Oncology definition), an increase of 2.0 ng/mL above the nadir after radiotherapy (Phoenix definition), or a level of 0.2 ng/mL and increasing after prostatectomy (American Urological Association definition).

bioinformatics: also known as computational biology. The use of techniques from applied mathematics, informatics, statistics, and computer science to solve biologic problems.

biologically active dose range: the range of drug doses required for sufficient modulation of the cellular target.

biomarker: a functional biochemical or molecular indicator of a biologic or disease process that has predictive, diagnostic, and/or prognostic utility.

biomarker (biologic marker): a functional biochemical or molecular indicator of a biologic or disease process that has predictive, diagnostic, and/or prognostic utility.

biomarker classifiers: a diagnostic or prognostic classifier that is based on biomarker components. The classifier is used to select or stratify patients for treatment. The biomarker components need not be validated measures of disease status, as used in the sense of the US Food and Drug Administration for surrogate end points or early detection biomarkers. See classifiers.

bioreductive drugs: drugs that become activated under hypoxic conditions to produce toxic metabolites.

biotin: formally known as vitamin H of the B2 complex. Biotin can be isolated from raw egg whites and is a growth factor for most yeasts and an essential cofactor in humans.

bispecific antibody: see bispecific monoclonal antibody.

bispecific monoclonal antibody: a modified monoclonal antibody that has two binding arms, one to a tumor antigen and the other to a hapten.

bisulfite modification: see bisulfite sequence analysis.

bisulfite sequence analysis: DNA treated with sodium bisulfite before sequence determination converts unmethylated cytosines in DNA to deoxyruracils, leaving methylated cytosines unchanged. The pattern of methylated cytosines in the final sequence of the DNA is assessed by polymerase chain reaction by using specific primers followed by sequence analysis.

bivalent hapten: two incomplete, covalently linked antigens that are incapable of causing the production of antibodies but capable of combining with a specific antibody.

BKV (BK virus): a human polyomavirus. Infection with JCV and BKV is prevalent in the human population, although the mode of transmission is not clear. BKV and JCV exist as unapparent infections in immunocompetent hosts but can produce pathologic effects in immunocompromised individuals through the destruction of infected cells. BKV has been associated with renal nephropathy, affecting as many as 5% of renal transplant recipients.

blood cell RNA expression: provides a snapshot of the genes expressed in blood cells at specific points in time. This snapshot can be acquired by screening throughout the treatment period. Using mathematical algorithms, the extent of a particular gene expression can be used to predict response to a certain therapy.

Bmi-1 protein: a product of the BMI1 (B-cell–specific Moloney murine leukemia virus insertion site 1) gene. The Bmi-1 protein is homologous to the polycomb group proteins, which regulate gene expression by altering chromatin structure.

BMS-214662: a farnesyltransferase inhibitor. See FT inhibitors.

BMS-354825: a tyrosine kinase inhibitor designed to inhibit the ATP-binding site of the Src and Abl kinases.

bone resorption: the process of losing bone substance. Bone, when it is remodeled (reshaped), undergoes both new formation and resorption. The cell responsible for the resorption of bone is called an osteoclast, and the bone-forming cell is the osteoblast.

Bonferroni correction: a simple statistical procedure to adjust the P value for multiple comparisons. The correction is based on the idea that if an experimenter is performing n different comparisons on a set of data, then one way of maintaining the familywise error rate at a given level (eg, P < .05) is to test each individual hypothesis at a statistical significance level of P/n. The Bonferroni correction controls the probability of a type I error (false positives) only and comes at the cost of increasing the probability of a type II error (false negatives). When large numbers of comparisons are performed (ie, microarray analysis), the test becomes impractical and too conservative, and therefore, permutation-based methods are favored. See false discovery rate (FDR).

bootstrap procedure: a nonparametric statistical method to estimate sampling distributions of an estimator by resampling with a replacement from the original sample. In prognostic research, the bootstrap helps to obtain an impression of the validity of predictions in new but similar patients.

bootstrap resampling technique: an analytical tool that evaluates how robust the associations are between the specimens under evaluation on the basis of the gene profiles. The higher the number provided by this method, the more robust the associations.

bortezomib: formerly called PS-341. Bortezomib (also known as Velcade [Millennium, Cambridge, MA]) is a modified dipeptidyl boronic acid derivative that is developed as a reversible inhibitor of the protease activity of mammalian proteasome. See proteasome.

B-Raf: see Raf.

BRAF: an isoform of RAF. See Raf.

BRAF V600E: the most common oncogenic mutation of BRAF in cancer. The V600E amino acid change results in constitutive activation of the BRAF kinase and promotes cell transformation.

BRCA-ness: a term applied to breast cancers, referring to the degree of relationship of a given breast cancer to one deficient in the BRCA1 gene.

BRCA1: a tumor suppressor gene known to play a role in repairing DNA breaks. Mutations in this gene are associated with increased risks of developing breast or ovarian cancer.

BRCA1 expression: see BRCA1.

BRCA2: a tumor suppressor gene whose protein product is involved in repairing chromosomal damage. Although structurally different from BRCA1, BRCA2 has cellular functions similar to BRCA1. BRCA2 binds to RAD51 to fix DNA breaks caused by irradiation and other environmental agents. Also known as the breast cancer 2 early onset gene.

breadth of coverage: the amount of genomic territory sequenced in a given testing modality.

brentuximab vedotin: an antibody-drug conjugate that consists of the chimeric immunoglobulin G1 antibody cAC10, specific for human CD30; the microtubule-disrupting agent monomethyl auristatin E; and a protease-cleavable linker that covalently attaches monomethyl auristatin E to cAC10.

Breslow's tumor thickness: the microstage of malignant melanoma is defined by Breslow's and Clark's classifications. The Breslow classification defines the absolute vertical thickness in mm of the primary tumor in the skin. This microstaging more accurately predicts subsequent behavior of cutaneous melanoma.

BRG: gene that encodes a member of the Swi/Snf family of proteins with helicase and ATPase activities, which are believed to alter the chromatin structure around genes whose transcription they regulate.

Brm: a member of the Swi/Snf family of chromatin remodeling complex. Because of its helicase and ATPase activities, Brm increases gene accessibility by overcoming the repressive effects of nucleosomal histones.

bromodomains: motifs found in transcription factors. Bromodomains bind to the acetyl-lysine group, a modification that is seen in histones. They play a role in anchoring HAT (histone acetyl transferase) and other coactivator proteins to active chromatin. Bromodomains are involved in reading the histone code by binding acetylated histone tails.

BTB/POZ (bric á brac, tramtrack, broad complex/pox virus zinc finger) domain: conserved motif, present in transcriptional repressors, that mediates protein dimerization/multimerization and interaction with transcriptional co-repressors.

BTBD3: gene coding for the BTB (POZ) domain containing 3 protein whose function is yet unknown.

BTK (Bruton's tyrosine kinase): a B-cell signaling kinase best known for its involvement in B-cell receptor (BCR) signaling. BTK mutations are the cause for X-linked agammaglobulinemia, a rare primary immunodeficiency.

BTK inhibitor: kinase inhibitors that function either as reversible, ATP-competitive agents or as irreversible kinase inhibitors that covalently bond to their target. Irreversible BTK inhibitors, such as ibrutinib, exhibit high selectivity, prolonged pharmacodynamics, and potency in overcoming endogenous ATP competition.

BUM (beta-uniform mixture analysis): a model used to quickly compute the false discovery rate estimates for the analysis of microarray data by taking the distribution of individual P values to follow a mixture of a beta density function from the genes that differentially expressed and a uniform density function from the genes that are not differentially expressed.

bystander effect: the biologically positive response observed in untreated cells when neighboring cells are treated. Because of the bystander effect, the magnitude of the therapeutic response exceeds the effect expected from direct target-cell treatment, illustrating that the treatment not only induces direct cytotoxic effects against the individual target cell but also causes the growth suppression of bystander, untreated cells via other mechanisms.


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