G1 arrest: arresting cells in the G1 phase of the cell cycle, which is an ordered cycle of complex events, resulting in cell division. The GAP1 and GAP2 stages are separated by the S (DNA synthesis) and M (mitosis) phases, respectively.
GADD45: a gene whose expression is upregulated during DNA damage and/or growth arrest. GADD45 is supposed to be involved in DNA repair mechanisms.
GADPH: gene coding for glyceraldehyde-3-phosphate dehydrogenase, an enzyme belonging to the glycolytic pathway. GADPH is a ubiquitously expressed cellular enzyme. This gene is often used as a reference (housekeeping) gene for normalization of reverse transcriptase polymerase chain reaction data.
GAGE: a family of genes expressed in various tumors and in testis that codes for tumor-associated antigens that are presented by human leukocyte antigen class I molecules and recognized by T cells.
galectin-1: a member of the family of galectinsanimal lectins characterized by conserved carbohydrate recognition domains and binding affinity for β-galactosidases. Galectins are involved in intracellular signaling after binding to glycoproteins/glycolipids on cell surfaces and in the extracellular matrix. Found in invasive tumor environments, galectins play a role in pathologic processes, including proliferation, cell aggregation, adhesion, migration, apoptosis, and immunoregulation.
GATA1: a member of the family of erythroid cell-specific transcriptional factors that regulate erythroid development. See transcriptional regulatory complexes.
GATA3: a member of the GATA family of transcription factors. GATA3 is abundantly expressed in the T-cell lineage and possibly participates in T-cell receptor gene activation via enhancer binding.
GBP1: gene coding for the interferon-induced GTP-binding protein 1.
GD3 ganglioside: a carbohydrate-rich sphingolipid that contains sialic acid. GD3 ganglioside is synthesized during the onset of apoptotic signaling. GD3 ganglioside is an attractive target for immunotherapy of melanoma because it is expressed abundantly on all melanomas but not expressed on most healthy tissues.
gefitinib: a member of the class of tyrosine kinase inhibitors. Gefitinib (also known as Iressa, AstraZeneca, London, United Kingdom) binds to the cytoplasmic region of the epidermal growth factor receptor (EGFR) that also binds ATP. By competing with ATP binding that is essential for tyrosine phosphorylation, gefitinib inhibits activation of EGFR and blocks the cascade of reactions leading to cellular proliferation.
gelatin zymography: a technique that allows for assaying the enzymatic activity of a protein suspected of being a protease, including proteins belonging to the class of matrix metalloproteinases. Typically, the sample suspected of containing the proteases is electrophoresed in polyacrylamide gels containing the substrate (type III gelatin or b-casein) that can be degraded by these enzymes, the SDS gel removed after electrophoresis, and the proteolytic proteins visualized as clear bands against the Coomassie blue-stained protein background.
geldanamycin: a benzenoid ansamycin class of agents developed to bind to heat shock proteins and inhibit their chaperone function. Unacceptable hepatotoxicity associated with the drug was responsible for terminating its development.
gelsolin: a calcium-regulated, actin-modulating protein. Gelsolin caps actin filaments and promotes the assembly of actin monomers. It also promotes the assembly of actin monomers to actin filaments. Thus gelsolin controls the organization of the actin cytoskeleton in cells and controls cell morphology, motility, signaling, and apoptosis.
genasense: an antisense oligodeoxynucleotide against Bcl-2. Genasense downregulates Bcl-2, a potent inhibitor of apoptosis. Genasense is being evaluated for the treatment of melanoma and several hematologic malignancies in which Bcl-2 expression has been implicated in disease resistance. See antisense oligonucleotides.
gene amplification: the presence of multiple copies of a gene or genes that leads to overexpression of that gene or gene.
gene array: a microchip on which DNA sequences for many genes are embedded. A gene array is used to measure gene expression of many genes simultaneously.
gene cluster: a group of genes that show coordinated expression (ie, if one gene is highly expressed, all other members of the gene
cluster are also expected to have high expression values) in a group. The strength of this coordinated expression can be measured by the coexpression correlation coefficient between the genes
gene expression analysis: a technique for the simultaneous quantification of the mRNA expression level of thousands of genes. Gene expression analysis can be performed using microarrays, reverse transcriptase polymerase chain reaction, or other technologies for measuring gene expression.
gene expression profile: the expression of a set of genes in a biologic sample (eg, blood, tissue) using microarray, reverse-transcriptase polymerase chain reaction, or other technology capable of measuring gene expression.
gene expression profiling: identifying the expression of a
set of genes in a biologic sample (eg, blood, tissue) using microarray
gene ontology: allows for annotating genes and their products with a limited set of attributes. The three organizing principles are molecular function, biologic process, and cellular component. The development of structured, controlled vocabularies (ontologies) that describe gene products in terms of these organizing principles in a species-independent manner is a constantly evolving process.
Gene Set Enrichment Analysis (GSEA): a computational method that determines whether an a priori defined set of genes shows statistically significant, concordant differences between two biologic states.
gene signature: the coordinated response of many genes to a particular stimulus; for example, the myc oncogene signature is the response of many genes to the forced overexpression of the myc oncogene.
genetic algorithm: a type of iterative mathematical modeling technique used to find the optimal combinatorial state given a set of parameters of interest. Usage of the
term genetic refers to the mechanism of the algorithm where, through the process of iteration, individual models evolve over time and compete with each other in a Darwinian fashion in which the fittest model emerges as the solution, similar to how chromosomes
evolve to create speciation. Given a set of parameters of interest, a baseline model is fit from a subset of the eligible variables, each dichotomized
around a random cut point. Then, through successive iterations, the model is altered by either swapping one of the included parameters (a crossover) or by changing the dichotomization cut point for an included parameter (a mutation), and the models fitness is reassessed.
After several million iterations, the model with the best goodness of fit is selected.
genetic polymorphisms: a genetic variant seen in at least 1% of the population. Because proteins are gene products, their polymorphisms reflect allelic differences in the gene. The advent of restriction enzymes, which digest DNA to fragments based on sequence specificity, has ushered in an era of restriction fragment length polymorphisms in which changes in DNA sequences manifest as restriction fragments of different sizes when cleaved with a specific restriction enzyme. Polymorphisms are used in tissue typing, in determining disease, in pharmacogenetics, and in assessing genetic diversity.
genetically engineered mouse: a mouse model in which the genetic makeup of the mouse has been modified by transgenic or gene-targeting technologies to affect expression of a gene of interest or to express a mutation.
genetically engineered mouse model: a model in which the genetic make-up of the mouse has been modified by transgenic or gene-targeting technologies to affect expression of a gene of interest or to express a mutant.
genome: the complete set of genetic material.
genome-testing modality: the technology or platform that is used to translate biologic tissue into genetic or molecular data, including Sanger sequencing, mass spectrometric genotyping, allele-specific polymerase chain reaction–based technologies, and massively parallel sequencing, among other options.
genome-wide association study: hypothesis-free studies that evaluate the association of genetic variations throughout the entire genome with traits, using high throughput genotyping technologies to assay single nucleotide polymorphisms.
genomic classifier: supervised machine learning model for mapping a panel of gene or RNA expression signatures to prognostic classes.
genomic scarring: subchromosomal DNA copy number gains and losses that are thought to reflect defective repair processes at some point in the life of a neoplasm.
genomic signatures: the expression of a set of genes in a biologic sample (eg, blood, tissue) using microarray technology.
genomics: the scientific discipline in which multiple genes, gene products, or regions of the genome are analyzed via large-scale, high-throughput molecular approaches directed to DNA and RNA. This definition is a deviation from that of the original term, which meant an analysis of the whole genome.
genotype: the specific genetic makeup of a given individual. Although genotypes give rise to the phenotype of an individual, genotypes and phenotypes are not always correlative. For example, some genotypes are expressed only under specific environmental conditions.
genotype-phenotype correlation: the relationship between the presence of an individual genotype and the resulting physical trait (eg, biochemical reaction, morphology, behavior, pattern of abnormalities, drug response).
genotyping: the process used for obtaining the genotype of a given gene. From a somatic point of view (within a tumor), genotyping can be used to identify a predetermined genetic aberration,
such as somatic mutations, copy number variations, gene expression changes, and/or DNA methylation. Genotyping identifies only predetermined aberrations; all other aberrations are
geranylgeranyltransferase: an enzyme that covalently adds a geranylgernanyl group (a 20-carbon moiety) to a protein. See prenylation.
germinal center B-cell–like: a subtype of diffuse large B-cell lymphoma (DLBCL). One of the two major subtypes of DLBCL identified by gene expression profiling. This subtype is also referred to as germinal center B-cell type in immunohistochemistry-based classifications.
germline alterations: alterations in a gene present at conception that are incorporated into every cell of an individual.
germline mutation: an inherited variation in the lineage of germ cells. Germline mutations can be passed on to offspring.
germline polymorphism: a difference in DNA sequence among individuals in the germ cells.
Unlike somatic cell genetic mutations, these polymorphisms can be transmitted to an organisms offspring. Genetic polymorphisms may be the result of a chance process or may have been induced by external agents (such as viruses or radiation). Changes in DNA sequence that have been confirmed to be caused by external agents are generally called mutations rather than polymorphisms.
GFAP (glial fibrillary acidic protein): a member of the intermediate filament family that provides support and strength to cells. Several molecules of GFAP bind together to form the primary intermediate filament found in astrocytes.
Gleason score: a pathologic description of prostate cancer grade on the basis of the degree of abnormality in the glandular architecture. Gleason patterns 3, 4, and 5 denote low, intermediate, and high levels of histologic abnormality and tumor aggressiveness, respectively. The score assigns primary and secondary numbers on the basis of the most common and second most common patterns identified.
GLI1 (glioma-associated oncogene family zinc finger 1): a transcription factor that is activated by the hedgehog signaling cascade. It is involved in cell proliferation and differentiation during embryonic development and tumorigenesis.
glioblastoma multiforme (GBM): by far the most common and most malignant of the glial tumors. Composed of a heterogenous mixture of poorly differentiated neoplastic astrocytes, glioblastomas primarily affect adults, and they are located preferentially in the cerebral hemispheres. Much less commonly, GBMs can affect the brainstem in children and the spinal cord. These tumors may develop from lower-grade astrocytomas (WHO grade II) or anaplastic astrocytomas (WHO grade II), but more frequently, they manifest de novo, without any evidence of a less malignant precursor lesion. The treatment of glioblastomas is palliative and includes surgery, radiotherapy, and chemotherapy.
glomerular filtration rate (GFR): the measure of fluid filtered from the renal glomerular capillaries into the Bowmans capsule per unit time. GFR is often used to determine renal function.
GLUT1: the glucose transporter type 1. GLUT1 is ubiquitously expressed and is important for constitutive, basal glucose transport. The transporter is widely distributed in fetal tissues and predominantly expressed in endothelial
cells, erythrocytes, and the blood brain barrier in adults. GLUT1 is found to be an important mediator of glucose influx in most cancer cells, and the increased expression enables cancer cells to maintain high growth rates and metabolic activity.
glycan: a polysaccharide or oligosaccharide.
Glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.
glycolysis: the enzymatic breakdown of a carbohydrate (as glucose or glycogen) with the production of pyruvic acid or lactic acid and the release of energy stored in the high-energy phosphate bonds of ATP.
GlyCOSyltransferase: the class of enzymes that transfer sugar molecules (eg, glucose, galactose) to amino acids in proteins, several different lipid molecules, and carbohydrates, with specificity of the enzyme residing in the sugar molecule transferred, molecule glycosylated, and coenzymes that act as carriers of the sugar molecule.
GM-CSF (granulocyte macrophage colony-stimulating factor): a growth factor that stimulates the production of white blood cells. Normally used in cancer therapy and bone marrow transplantation, GM-CSF augments WBC production, decreasing the risk of infection. In vaccine therapy, it is an effective vaccine adjuvant administered to activate endogenous dendritic cells, the most effective antigen-presenting cells of the immune system.
GNAT: histone acetyltransferases belonging to the GNAT (Gcn5-related N-acetyltransferase) superfamily are grouped on the basis of their similarity in several homology regions and acetylation-related motifs.
GNB2L1: gene encoding for the guanine nucleotide-binding protein beta subunit-like protein, which is a receptor of activated protein kinase C.
goodness of fit: this is a coefficient, termed R2, with values between 0 and 1. A value of 1 means that all the interpatient outcome variation is perfectly explained by the multivariate model. A value of 0 means that the model does not explain the differences between individual patients at all.
Gorlin syndrome: also called nevoid basal cell carcinoma syndrome. A genetic syndrome caused by mutation of the PTCH1 gene and rarely by mutation of SUFU that predisposes individuals to multiple basal cell carcinomas, odontogenic keratocysts, palmar or plantar pits, and falx cerebri calcification. Can also predispose to vertebral/rib abnormalities, cleft lip/palate, medulloblastomas, macrocephaly, polydactyly, ovarian/cardiac fibromas, lympho-mesenteric or pleural cysts, and ocular anomalies.
(-)-gossypol: negative enantiomer of a polyphenolic molecule derived from the cotton plant. Having male contraceptive properties, it is a natural compound known to inhibit Bcl-2 and Bcl-xL function via targeting their BH3-binding domain. (-)-Gossypol is currently entering clinical trial for
gp100: a melanocyte differentiation antigen that is shared between melanomas and melanocytes, which is the origin of melanomas. It is a matrix protein involved in melanin synthesis. gp100 protein expression is detected by the gp100-specific antibodies HMB-45 and NKI-beteb.
GPCR (G-proteincoupled receptors): characterized by seven transmembrane segments. GPCR respond to a wide variety of responses, including light, amines, hormones, neurotransmitters, and proteins. Agonists binding to the extracellular loops or transmembrane regions have been reported. On the basis of sequence similarity and function, GPCR are classified into five different families.
Grb2 (growth factor receptor bound protein 2): an adapter protein involved in signal transduction pathways governed by protein tyrosine kinases. The single SH2 (Src-homology 2) domain in Grb2 recognizes phosphotyrosine-containing domains in receptor tyrosine kinases such as the epidermal growth factor receptor and platelet-derived growth factor, on docking proteins such as Sch and on nonreceptor tyrosine kinases such as FAK. SH3 (src-homology 3) domains that flank the single SH2 domain bind to proline-rich regions of SOS, a GDP releasing factor.
GRB7: gene encoding growth factor receptor-bound protein 7, which belongs to the GRB family of proteins (eg, GRB2, GRB10, and GRB14). GRB7 functions in mitogenic signaling and is an important component of insulin and insulin-like growth factor and epidermal growth factor receptor signal transduction pathways.
GRP94: a homolog of HSP90. See HSP90.
GST (glutathione-S-transferase): a family of enzymes that play an important role in detoxification. On the basis of their biochemical, immunologic, and structural properties, GSTs are classified into four main classes: α (alpha), μ (mu), π (pi), and ϑ (theta).
GSTM1: a member of the family of enzymes called glutathione-S-transferase, which plays an important role in detoxification. The μ(mu) class has distinct biochemical, immunologic, and structural properties from members of the other classesα (alpha), π (pi), and ϑ (theta). See GST (glutathione-S-transferase).
GSTP1 (glutathione s-transferase p1): a member of a family of enzymes that play an important role in detoxification. GSTP1 catalyzes the conjugation of many compounds with reduced glutathione. See GST (glutathione-S-transferase).
GUS: gene coding for β-glucuronidase, an enzyme that hydrolyzes a variety of conjugated glucuronides and has ubiquitous cellular expression. The coding sequence is used in a variety of expression vectors in which the GUS gene acts as a reporter gene to help evaluate the efficiency of expression of a foreign gene. GUS is also used as a reference (housekeeping) gene to normalize reverse transcriptase polymerase chain reaction data.
GVAX: a cancer vaccine that is made of tumor cells genetically engineered to produce granulocyte macrophage colony-stimulating factor (GM-CSF). Tumor cells are engineered with adenovirus type 5–containing deletions in the E3 and E1 regions, with GM-CSF being cloned into the E1 region of the adenovirus genome. The vaccine is thus replication defective. See GM-CSF (granulocyte macrophage colony-stimulating factor).