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Oncology Glossary

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hamartin: the protein product of the tuberous sclerosis 1 (TSC1) gene. Hamartin binds directly to tuberin, the GTPase that inactivates Rheb. Mutations in TSC1 or TSC2 lead to the same disease phenotype, suggesting that hamartin and tuberin are both required for the proper functioning of the tuberin-hamartin heterodimers. Phosphorylation may regulate both the formation of the heterodimer and the activity of the tuberin-hamartin complex.

haplotype: a set of closely linked genetic markers present on one chromosome that tend to be inherited together. Some haplotypes may be in linkage disequilibrium.

haplotype-tagging single nucleotide polymorphisms: markers that are statistically associated with and therefore considered to be representative of a set of single nucleotide polymorphisms within a particular region. Using this technique, the identification of a few alleles of a haplotype block allows for the identification of all other polymorphic sites in this region of linkage disequilibrium.

HapMap: an international project that created a publically available genome-wide database of common human sequence variations (http://hapmap.ncbi.nlm.nih.gov).

hapten: an incomplete antigen, typically a small molecular weight substance, being incapable of causing the production of antibodies but capable of combining with a specific antibody.

Hardy-Weinberg equilibrium: a state in which genotype frequencies and ratios remain constant from generation to generation and in which genotype frequencies are a product of allele frequencies. A randomly mating population tends toward a Hardy-Weinberg equilibrium state if there are no mutations, migrations, or environmental factors favoring particular genotypes.

HATs (histone acetyl transferases): enzymes that acetylate histone tails and transcription factors, facilitating transcriptional activation.

hazard ratios: the ratio of the hazard rate in one group (for example, a group of treated patients) to the hazard rate in another group (for example, an untreated control group of patients). The hazard rate is the probability of a specified event, such as death or cancer recurrence, occurring during a short time interval. The hazard ratio, therefore, is a measure of the relative probability of an event occurring at any given point in time.

HDAC (histone deacetylase) inhibitors: inhibit the activity of HDAC. See HDACs (histone deacetylases).

HDAC inhibitors: inhibit the activity of HDACs. See HDACs (histone deacetylases).

HDACs (histone deacetylases): enzymes that catalyze the removal of acetyl groups from the post-translationally modified acetylated amino functions of lysine residues in histones and nonhistone proteins. HDACs act as remodeling factors and may act as transcriptional repressors. Classification of HDACs is based on sequence homology to yeast HDAC.

HDI (HER dimerization inhibitor): an inhibitor of tumor growth and survival that functions by inhibiting HER dimerization.

health-related quality of life (HRQoL): a broad multidimensional concept that usually includes self-reported measures of physical and mental health.

heat shock proteins: a general class of proteins important for cell viability that are typically expressed in response to stress. Heat shock proteins act as molecular chaperones for other proteins that have important regulatory roles in refolding denatured proteins, transporting proteins intracellularly, and preventing protein unfolding and aggregation.

helical tomotherapy: intensity-modulated radiation therapy technology in which a high-energy x-ray (photon) fan beam is modulated as it rotates around a patient while the patient is simultaneously translated along the axis of beam rotation. Treatment localization is verified prior to treatment by megavoltage computed tomographic imaging.

helicase: a protein that unwinds DNA at replication forks.

helper peptide: a peptide that binds to class II MHC molecules and thereby creates an epitope recognized by CD4+ helper T cells.

hemimethylated DNA: DNA methylated on one strand only.

hepatocellular carcinoma (HCC): a type of adenocarcinoma; the most common form of liver cancer.

HER: see HER2⁄neu (human epidermal growth factor receptor 2), EGFR (epidermal growth factor receptor), and ErbB.

HER1: see ErbB.

HER1/EGFR: see ErbB.

HER1/ErbB1: see ErbB.

HER2/CEP17: the number of copies of the HER2 gene divided by the number of copies of chromosome 17 (strictly the number of copies of the pericentric region of chromosome 17 to which the CEP17 fluorescent in situ hybridization probe hybridizes).

HER2/neu/ErbB2: see ErbB.

HER2/neu (human epidermal growth factor receptor 2): also called ErbB2. HER2/neu belongs to the epidermal growth factor receptor (EGFR) family and is overexpressed in several solid tumors. Like EGFR, it is a tyrosine kinase receptor whose activation leads to proliferative signals within the cells. On activation, the human epidermal growth factor family of receptors are known to form homodimers and heterodimers, each with a distinct signaling activity. Because HER2 is the preferred dimerization partner when heterodimers are formed, it is important for signaling through ligands specific for any members of the family. It is typically overexpressed in several epithelial tumors.

HER3: a member of the epidermal growth factor receptor family of receptor tyrosine kinases that is encoded by the ErbB3 gene. HER3 has a ligand binding domain but does not have an active kinase domain. HER3 heterodimerizes with HER2 and other members of the epidermal growth factor receptor family with active kinase domains to drive cell proliferation, transformation, and malignant pathogenesis. See ErbB.

HER3/ErbB3: see ErbB.

HER4: see ErbB.

HER4/ErbB4: see ErbB.

HercepTest: an immunohistochemical assay for human epidermal growth factor receptor overexpression in carcinomas to determine whether patients could benefit from treatment with trastuzumab.

hereditary nonpolyposis colorectal cancer (HNPCC): cancer subtype accounting for 5% of all colorectal cancer. HNPCC arises as a result of a hereditary defect in one of the mismatch repair genes. Cancer of the uterus (ie, womb or endometrium), GI tract (ie, stomach, small intestine, or pancreas), urinary system (ie, kidney or ureter), and female reproductive organs (ie, ovary) may be cancers seen in some HNPCC families. A family history, colon examination, and genetic testing for mutations in DNA mismatch repair genes are helpful in identifying HNPCC.

heregulin: belongs to a family of proteins known to activate ErbB2 in association with ErbB3 and ErbB4.

HETE (hydroxyeicosatetraenoic acid): a major product of arachidonic acid metabolism and a metabolic intermediate in the synthesis of leukotrienes.

heterochromatin: a chromatin structure consisting of nucleosomes tightly wound in a solenoid fashion along with accessory proteins. In this configuration, the DNA in nucleosomes is inaccessible to the transcription machinery.

HGF (hepatocyte growth factor): a growth factor with strong mitogenic activity on hepatocytes and primary epithelial cells through its interaction with its receptor (c-met). HGF has multifunctional activities that regulate cell growth and motility.

HGS-ETR2: a monoclonal antibody currently in developmental stages designed to function as an agonist for TRAIL-R2. By binding to TRAIL-R2, HGS-ETR2 induces apoptosis in preclinical studies in xenograft tumor models.

hierarchical clustering: an analytical tool used to find the closest associations among gene profiles and specimens under evaluation.

HIF (hypoxia-inducible factor): a transcriptional factor that regulates the adaptive responses of mammalian cells to low oxygen (hypoxia). It is composed of HIF-1α, which is upregulated in conditions of hypoxia, and HIF-1β (or aryl hydrocarbon receptor nuclear translocators), which is expressed constitutively. Dimerization of HIF-1α with HIF-1β leads to transcription of genes such as VEGF and PDGF.

HIF-1α (hypoxia-inducible factor 1α): a component of hypoxia inducible factor (HIF). See HIF (hypoxia-inducible factor).

HIF-2α (hypoxia-inducible factor 2α): a member of the same family of transcription factors regulated by hypoxia.

high-grade prostatic intraepithelial neoplasia (HGPIN): the only accepted precursor of prostate cancer characterized by morphologic and molecular abnormalities that are intermediate between benign prostatic epithelium and cancer. High-grade prostatic intraepithelial neoplasia is associated with concurrent or subsequent prostate cancer.

histologic grade: provides prognostic information in many tumors, including ovarian cancer. Histologic grade is based on a combination of cellular features (nuclear, cytologic, and architectural). The more nuclear atypia and mitotic figures, the higher the grade.

histologic type: determined by microscopic examination of the cell morphology and architecture of tissues.

histone code: the concept that transcriptional complexes interpret modifications in histone tails.

histone demethylases: enzymes that remove the methyl group from methylated histones, facilitating repression of gene expression.

histone methyltransferases: enzymes that catalyze the transfer of methyl groups from S-adenosylmethionine to lysine and arginine residues of histone proteins. The activity is sometimes associated with EZH2 proteins. See EZH2.

histone modifying enzymes: enzymes that covalently modify histones.

histopathologic: the examination of a biopsy or surgical specimen by a pathologist, after the specimen has been processed and histologic sections have been placed onto glass slides. The vast majority of cancer diagnoses are made by pathologists. The medical diagnosis is formulated as a pathology report describing the histologic findings and the opinion of the pathologist. Evaluation of the diagnosis and the prognosis is required for most treatment protocols.

histopathologic response: tumor regression assessed semiquantitatively according to a recently published scoring system. Histopathologic regression defines the percentage of residual tumor compared with the tumor bed.
Regression score 1A: no residual tumor
Regression score 1B: less than 10% residual tumor
Regression score 2: 10%-50% residual tumor
Regression score 3: more than 50% residual tumor
Regression scores 1A and 1B are defined as histopathologic response.
Regression scores 2 and 3 are defined as histopathologic nonresponse.

HLA (human leukocyte antigen): the human major histocompatibility complex, which is expressed as two sets of highly polymorphic cell surface molecules, termed HLA class I and HLA class II. HLA class I molecules are expressed on all nucleated cells and are encoded by diverse alleles of the HLA-A, HLA-B, or HLA-C genes (eg, HLA-A1 [HLA molecule encoded by the A1 allele of the HLA-A gene] and HLA-B7 [HLA molecule encoded by the B7 allele of the HLA-B gene]). HLA class I molecules bind peptides derived from cellular proteins upon processing. Cytotoxic T lymphocytes, expressing the CD8 coreceptor, recognize cell-bound peptides in association with HLA class I molecules on target cells.

HLA/peptide tetramers: multimerized human leukocyte antigen (HLA)/peptide molecules consisting of four soluble and biotinylated HLA molecules with bound peptides that are linked to fluorochrome-labeled streptavidin. On the basis that HLA/peptide tetramers bind specifically to T-cell receptors on human T lymphocytes, they are used to detect and isolate antigen-specific T cells independent of their cytokine secretion profile.

HLA.DPB1: gene encoding the major histocompatibility complex, class II, DP beta 1. HLA.DPB1 functions in antigen presentation.

HLA-DR: human class II histocompatibility antigen present on several cell types, including antigen-presenting cells, B cells, monocytes, macrophages, and activated T cells.

hMLH1: human MLH1. See MLH1 (Mut L homolog 1).

hMSH2 (human mut S homolog 2): an integral component of the DNA mismatch repair pathway. The protein coded by the gene binds to mispairs and insertion/deletion loops in DNA and is responsible for fidelity of DNA replication.

homologous recombination: genetic recombination whereby nucleotide sequences are exchanged between two similar or identical strands of DNA to facilitate accurate repair of DNA double-strand breaks.

homozygosity: the presence of the same alleles at a particular gene locus on homologous chromosomes.

hospice: care provided by an interdisciplinary team that focuses on addressing symptoms and maximizing quality of life.

hot flash symptom severity score (HFSSS): the product of the number of hot flashes experienced during one 24-hour period and their severity (mild, moderate, severe). A weekly mean score is then calculated.

hot spots: sites in a specific gene known to harbor recurrent alterations that have well-defined biologic and/or clinical significance.

HOX (homeobox) genes: genes that encode the homeodomain proteins, which play important roles in the developmental processes.

HP1 (heterochromatin protein 1): a protein that helps fold and condense chromatin. The chromodomain of HP1 binds to methylated tails of histone 3, an interaction important for proper localization of HP1 to heterochromatin.

HPV E6: a protein that forms a complex with an E3 ubiquitin ligase, E6-associated protein (E6AP), and ubiquitinates the p53 tumor suppressor protein. The ubiquitination causes rapid degradation or destabilization of p53, thus resulting in deregulation of the cell cycle and proliferation, induction of cellular immortalization, and antiapoptosis.

HPV E7: a protein that binds to the cullin 2 ubiquitin ligase complex and ubiquitinates the retinoblastoma tumor suppressor protein. The ubiquitination causes rapid degradation or destabilization of the retinoblastoma tumor suppressor protein, thus resulting in deregulation of the cell cycle and proliferation, induction of cellular immortalization, and antiapoptosis.

H-Ras: see HRas.

HRas: an isoform of Ras. See Ras.

HRR (homologous recombination repair): a DNA repair pathway that repairs the broken ends of DNA by using information on the intact sister chromatid or homologous chromosome.

HSP90: a member of the family of heat shock proteins. HSP90 is important for cellular viability and acts as a molecular chaperone for other proteins by forming multimolecular complexes. These complexes are important regulatory elements in the fate of proteins, which include refolding of denatured proteins, intracellular transport of proteins, and preventing protein unfolding and aggregation. Although heat shock proteins are usually produced in response to stress (eg, heat, nutrient deprivation), HSP90 is typically expressed at high levels even under nonstress conditions.

Hs.seq.all, Hs.data, and LL_tmpl: UniGene (www.ncbi.nlm.nih .gov/UniGene) is an experimental system maintained at the National Center for Biotechnology Information for automatically partitioning GenBank sequences into a nonredundant set of gene-oriented clusters. Each UniGene cluster contains sequences that represent a unique gene as well as related information such as the tissue types in which the gene has been expressed and map location. Hs.seq.all contains all Homo Sapience sequences and the information included in clusters; Hs.data contains various information related to each UniGene ID; LL_tmpl contains various information related to each Locus ID.

Hu14.18-IL2: an immunocytokine, which is a fusion protein, comprising one molecule of humanized anti-GD2 monoclonal antibody, with an intact molecule of human interleukin-2 on the carboxy terminus of each immunoglobulin G heavy chain.

HuEx_1.0_st arrays (Affymetrix, Santa Clara, CA): microarrays that measure expression of individual exons.

human chorionic gonadotrophin (HCG): a hormone that is present during pregnancy. Levels of HCG in urine or blood are evaluated to confirm and monitor pregnancy and to diagnose trophoblastic disease or germ cell tumors. Blood levels of HCG are less than 5 IU/L in men and nonpregnant women and are not detected in urine samples (negative test results). In pregnant women, the levels increase as the pregnancy progresses and are also detected in a urine test. In nonpregnant adults, a high HCG value indicates tumors of the testicles or ovaries, the stomach, pancreas, large intestine, liver, or lung. High values in pregnant women may indicate a multiple pregnancy, an early pregnancy, or a fetus with Down syndrome. Low values in pregnant women may indicate an ectopic pregnancy or the death of the fetus.

human papillomavirus (HPV): a double-stranded DNA virus from the papillomaviridae family. Human papillomavirus is a cause of cervical cancer as well as of a subset of cancers of the anus, oropharynx, penis, vagina, and vulva.

human papillomavirus (HPV) tumor classification: a proposed system of classifying oropharyngeal tumors based on both HPV16 presence (as indicated by detection of HPV16 DNA) and cellular p16 expression status (as determined by immunohistochemistry or automated quantitative protein expression analysis). Proposed groups include class I (HPV16 negative/p16 nonexpressing), class II (HPV16 positive/p16 nonexpressing), and class III (HPV16 positive/p16 expressing).

humanized antibody: also commonly known as a CDRgrafted antibody. The humanized antibody is a monoclonal antibody that has been molecularly engineered to splice the antigen-binding domains of a murine antibody (ie, the CDRs [complementarity-determining regions]) onto human immunoglobulin framework.

humoral: pertaining to elements in the blood or other body fluids.

hybridoma: a cell line generated by fusing a B cell expressing a unique surface antibody of interest and a myeloma cell that does not produce an antibody by itself. The fusion cell line secretes the antibody of interest.

hypermethylation of CpG dinucleotide-rich promoter DNA sequences: see promoter hypermethylation and CpG island.

hypofractionation: fractionation scheme for delivery of ionizing radiation in which the dose per fraction is greater than 2 Gy or radiation treatment in which the total dose of radiation is divided into large doses and treatments are given less than once a day. Also called hypofractionated radiation therapy.

hypomorph: less-than-normal levels of expression of a wild-type gene.

hypoxia: oxygen concentration below normal physiological limits in a specific tissue.


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