validated assay: an assay that meets defined criteria for reproducibility, reliability, sensitivity, and accuracy.
validation: the process that tests the performance of a previously defined classifier or prognostic model on a new set of patients. For example, a gene expression signature classifier developed using data from one set of patients might be validated on another, independent set of patients.
validation set: samples used in evaluating the performance of a classifier. The validation set is formed by the units not used in developing the classifier (ie, the training set and test set).
variant: a change in the DNA sequence from the reference genome that may or may not have functional consequences.
variant calling: the method for identifying variants in a tumor sample.
vascular endothelial growth factor receptor (VEGFR): transmembrane tyrosine kinase receptors to which the VEGF ligand binds. VEGFR-1 (also called FLT1) and VEGFR-2 (also called KDR/FLK1[murine homologue]) are expressed on endothelial cells, whereas VEGFR-3 (also called FLT4) is expressed on cells of the lymphatic and vascular endothelium. VEGFR-2 is thought to be principally responsible for angiogenesis and for the proliferation of endothelial cells. Typically, most VEGFRs have seven extracellular immunoglobulin-like domains, responsible for VEGF binding, and an intracellular tyrosine kinase domain. See VEGF (vascular endothelial growth factor).
vascular endothelial growth factor (VEGF): a cytokine that mediates numerous functions of endothelial cells including proliferation, migration, invasion, survival, and permeability. VEGF is also known as vascular permeability factor. VEGF naturally occurs as a glycoprotein and is critical for angiogenesis. Many tumors overexpress VEGF, which correlates with poor prognosis. VEGF-A, -B, -C, -D, and -E are members of the larger family of VEGF-related proteins.
vascular normalization: the process whereby genetic or pharmacologic approaches result in pruning and/or remodeling of abnormal
tumor vessels, which become closer to normal tissue vasculature in terms of structure and function.
vasculogenesis: early development of the vascular system whereby new capillaries are formed. According to two separate proposals, the mechanisms that explain vasculogenesis are related to the sprouting of new capillaries from newly formed vessels (capillaries or veins) or new capillaries arising de novo from mesoderm-derived angioblasts.
VCAM (vascular cell adhesion molecule): a member of the superfamily of immunoglobulin-like molecules. VCAM is expressed on endothelial cells and regulates leukocyte migration across blood vessels. The molecule is a transmembrane protein that binds to a cytoskeletal protein within the cell and to the same (homophilic) or a different (heterophilic) protein present on another cell. It is also an anchor for the developing vasculature during angiogenesis.
VCAM-1: see VCAM.
VEGF inhibitor: inhibits vascular endothelial growth factor–induced signaling by blocking ligand binding to its cognate cell surface receptor or by blocking the kinase activity of the receptor. See VEGF (vascular endothelial growth factor).
VEGF-trap: engineered as a composite decoy receptor. The parental VEGF-trap was generated by fusing the first three immunoglobulin (Ig) domains of VEGFR-1 to the constant region of human IgG1. More potent VEGF-traps combine the constant region domain of human IgG1 with Ig domains from VEGFR-1 and VEGFR-2, thereby effectively preventing VEGF from binding to any of its cellular receptors. See VEGF (vascular endothelial growth factor).
VEGF-A, -B, -C, -D, -E: see VEGF (vascular endothelial growth factor).
VEGFR-1, -2, -3: see VEGFR (vascular endothelial growth factor receptor).
v-ErbB: one of two putative oncogenes encoded by avian erythroblastosis virus. v-ErbB encodes a truncated, constitutively active form of ErbB, and has been shown to cause erythroblastosis and sarcomas in chickens. The epidermal growth factor receptor is the cellular homolog of v-ErbB.
vertical growth phase (VGP): a phase of tumor progression in which melanoma cells form a nodule that invades the dermis.
VHL (von Hippel-Lindau): a tumor suppressor gene. Patients with von Hippel-Lindau (VHL) syndrome have mutations, allelic deletions, or silencing of the VHL gene. The phosphorylated or active VHL protein is a substrate recognition component of an ubiquitin-ligase complex that targets the hypoxia-inducible factor for proteolytic degradation. Loss of gene function permits the hypoxia-inducible factor to activate survival and proliferative cellular pathways.
vimentin: a flexible intermediate filament in the cytoplasm that maintains cell integrity and structure.
viral ABL: the oncogene encoded by the Abelson murine leukemia virus. It encodes a constitutively active nonreceptor protein tyrosine kinase. Aberrant activity of its cellular homologue, Abl, is found in several human leukemias.
viral load: using quantitative polymerase chain reaction, a starting concentration of template (eg, human papillomavirus) DNA can be determined. If human DNA concentration in the same tumor sample is also determined from a cellular
housekeeping gene (eg, β-globin), then simple arithmetic can be used to
determine viral load per human cell within the tumor sample.
virus-like particle assay (VLP assay): a test that uses particles similar to SV40 to detect the presence of SV40-specific antibodies.
virus-like particles (VLPs): structures resembling viruses.
VLPs are obtained by self-assembly of the viral capsid and/or envelope
proteins when expressed in heterologous systems including mammalian, insect, yeast and plant cells. VLPs do not contain any genetic material from the parental virus and are thus noninfectious, but their structural and antigenic properties are very similar to the wild-type viral particle. VLPs are used to develop serologic assays
and vaccines for noncultivable viruses.
vitamin D receptor: a member of the nuclear hormone-receptor superfamily of protein receptors. This intracellular receptor has both hormone-binding and DNA-binding domains. Upon binding by 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D, the
receptor complexes with the retinoic acid receptor. This heterodimer
subsequently recruits several coactivator molecules and binds to a DNA response element located in the promoter region of target genes to either activate or suppress transcription.
vorozole: a third-generation nonsteroidal aromatase inhibitor that has been evaluated in the treatment of breast cancer in postmenopausal women but is no longer under clinical development. See aromatase inhibitors.
VPF (vascular permeability factor): another name for the vascular endothelial growth factor. See VEGF (vascular endothelial growth factor).