dacarbazine DTIC: an alkylating agent that is used commonly for the treatment of melanoma, Hodgkin lymphoma, and soft-tissue sarcomas.
DAPK (death-associated protein kinase): a tumor suppressor gene whose gene product is a positive mediator of gamma-interferon&8211;induced programmed cell death. It shows serine-threonine kinase activity.
DC101: a monoclonal antibody against vascular endothelial growth factor receptor-2 that prevents the vascular endothelial growth factor from binding to vascular endothelial growth factor receptor-2, the receptor that is principally involved in angiogenesis. See VEGF (vascular endothelial growth factor) and VEGFR (vascular endothelial growth factor receptor).
DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging): a magnetic resonance imaging acquisition strategy involving multiple scans over a set volume during injection of a magnetic resonance contrast agent.
Deauville criteria: a reporting method that uses a five-point scale to assess glucose metabolism as a measurement of response to treatment in lymphoma.
decision curve analysis: an approach to evaluating the discrimination and calibration of different prognostic tests or models. A decision curve plots net benefit for a given model across a range of threshold probabilities. Net benefit is calculated as true positives minus false positives, with the false-positive term weighted by the threshold probability. The threshold
probability indicates the likelihood of a positive finding at which an intervention would be undertaken, given the results of the test or model.
decitabine: the nucleoside analogue 5-aza-2'-deoxycytidine (5-aza-2'-CdR), which is a DNA methyltransferase inhibitor. See DNA methyltransferase inhibitors.
decitabine (5-aza-2'-deoxycytidine): the nucleoside analogue 5-aza-2'-deoxycytidine (5-aza-2'-CdR), which is a DNA methyltransferase inhibitor. See DNA methyltransferase inhibitors.
decrescendo interleukin-2: a dosing protocol where the total interleukin-2 (IL-2) dose remains unchanged but is administered in a decrescendo schedule. An initial higher dose of IL-2 is administered in the first 24 hours and decreased progressively over subsequent days. Preclinical and clinical data indicate that decrescendo IL-2 dosing improves IL-2 efficacy and reduces its cumulative toxicity.
denaturing gradient gel electrophoresis (DGGE): a rapid mutation-scanning technology based on the melting characteristics of double-stranded DNA. On the basis of the fact that identical DNA molecules, which differ by only one nucleotide within a low-melting domain, will have different melting temperatures, DGGE is typically performed on polymerase chain reaction products. In the procedure, double-stranded DNA is electrophoresed through an acryl-amide gel containing a gradient of denaturant, which increases in the direction of electrophoresis. When appropriate denaturing conditions exist, the DNA molecules melt (melting domain). When the characteristic melting temperature is achieved, the aplicon melts and a single band is observed. Mismatched DNA (mutations) will retard the movement of the DNA through the gel, with sequence differences of one base having the ability to significantly alter the stability of the melting domains, and more than one band will be observed.
dendritic cells (DCs): the most efficient antigen-presenting cells of the immune system, which play a critical role in the regulation of the adaptive immune response. Immature DCs internalize and process antigens. Their maturation leads to DCs migrating to draining lymph nodes where they prime and activate T lymphocytes.
densitometric analysis: measuring the optical density of the bands appearing in blotting techniques (Northern, Southern, Western, etc) to semiquantify gene, mRNA, or protein expression.
deoxycytidine kinase: an important enzyme in the salvage reaction of nucleotide synthesis. Deoxycytidine kinase has broad substrate specificity and can catalyze the phosphorylation of deoxycytidine, deoxyguanosine and deoxyadenosine, using ATP or UTP as phosphate donors.
depth of coverage: the number of times a particular place
in the genome (eg, base, exon, or region) has been sequenced, often to ensure data accuracy and sensitivity.
desmin: a member of the type III family of intermediate filaments, a class of cytoskeletal elements. Desmin expression is muscle specific and found in skeletal, cardiac, and heart muscles but also in rhabdomyosarcoma, for which it serves as a general marker.
desmoplastic: the growth of dense connective tissue or stroma by transformation of fibroblastic-type cells to a myofibroblastic phenotype that stains positive for smooth-muscle actin. Furthermore, an increase in total fibrillar collagens, fibronectins,
proteoglycans, and tenascin C is distinctive of the desmoplastic
stromal response in several forms of cancer.
developmental studies: studies, analogous to phase II clinical trials, that first develop the classifiers. They should include an indication of whether the genomic classifier is promising and worthy of phase III evaluation.
DHEAS (dehydroepiandrosterone sulfate): a metabolite of dehydroepiandrosterone (DHEA), an androgen produced by the adrenal gland.
diagonal linear discriminant analysis: a mathematical form of classifier that combines the component features by a weighted linear average. With gene expression–based classifiers, the components are generally the logarithm of expression level of the selected genes. The weights are based on the degree of differential expression of the individual genes among the classes.
differential methylation hybridization (DMH): a high-throughput microarray technique designed to identify changes in DNA methylation patterns commonly observed in cancer and other disease states. DMH methodology comprises three fundamental components: the arraying of CpG island clones on glass slides, the preparation of the sample amplicons under investigation (using methylation-sensitive endonucleases, which digest nonmethylated DNA while leaving methylated DNA intact), and the hybridization of amplicon targets onto the CpG island microarray.
digital breast tomosynthesis (DBT): uses thin-slice reconstructions of the breast from multiple low-dose digital mammographic images acquired at multiple angles to create a pseudo- three-dimensional mammographic (x-ray) examination of the breast.
Dijkstra's shortest paths algorithm: a graph search algorithm that finds the path with lowest cost (ie, the shortest path) between a given node (or in the case of functional biologic networks, a given gene) and every other node.
dimerization inhibitors: inhibitors that prevent receptor dimerization after activation. Inhibition of receptor dimerization prevents downstream signal transduction important for cellular survival and proliferation.
dipeptidyl peptidase IV (DPP4): a cell membrane serine exopeptidase that cleaves dipeptides from the N terminus
of proteins. DPP4 is involved in the metabolic inactivation of
glucagon-like peptide-1 (GLP1).
diplotype: otherwise known as a haplotype pair, the subset of every single-locus genotype. Both genotype and diplotype represent the
types of chromosome pairs in each individual.
DISC (death-inducing signaling complex): a death complex containing Fas-associated death domain-containing protein (FADD), caspase-8, caspase-10, and most importantly, cellular FADD-like interleukin 1α-converting enzyme-inhibitory protein (c-FLIP).
discordant histology: the presence of two different lymphoma histologies concurrently in a patient (eg, diffuse large B-cell lymphoma in a lymph node but follicular lymphoma in the bone marrow).
discrimination: the ability to distinguish between patients with good and poor outcomes.
disease-free survival: the survival period spanning the time from surgery to a recurrence of cancer.
disease-specific survival rate: the percentage of people in a study who have not died from a specific disease
since diagnosis or treatment. Patients who died as a result of some other cause are not counted.
distance-weighted discrimination (DWD): a method to identify and adjust systematic biases that are present within microarray data sets. These systematic biases are a result of many
different experimental features including different microarray
platforms and different production lots of microarrays. DWD is useful in merging/comparing two tumor microarray data sets completed on different microarray platforms.
DM1: a derivative of maytansine 1 and a cytotoxic microtubule inhibitor trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic microtubule inhibitor DM1 and the human epidermal growth factor receptor 2targeted humanized monoclonal antibody trastuzumab. Also referred to as Kadcyla.
DNA adduct: an addition product with a chemical or metabolite bonded to DNA. DNA adducts can result in carcinogenesis.
DNA aptamer: a single-stranded DNA sequence that may vary in length from 25 nucleotides to 100 nucleotides. DNA aptamers can be formulated to bind to oligosaccharides, peptides, and proteins. They thus function as decoy molecules that may be agonists, antagonists, or enzyme inhibitors.
DNA-binding domains: a modular structure present in transcription factors that binds to specific DNA sequences in gene promoters and enhancers.
DNA methylation: methylation of bases contained in the DNA double helix, resulting in a loss of gene function. Generally occurring on cytosine residues in the DNA, methylation is important in regulating cell growth and differentiation and has resulted in the testing of DNA methyltransferase inhibitors as anticancer agents and differentiation agents.
DNA methyltransferase: enzyme that adds methyl groups from S-adenosyl methionine to bases in DNA strands after the replication of the DNA.
DNA methyltransferase inhibitors: inhibitors of the DNA methyltransferase enzyme, resulting in a loss of DNA methylation and a loss of gene silencing.
DNA-Seq: sequencing that determines the nucleotide sequence of DNA. The amount of DNA sequenced can be the full complement of genetic material in a specimen (whole genome) or a targeted portion of the genome (whole exome, specific genes, targeted regions, etc).
DNMT inhibitors: see DNA methyltransferase inhibitors.
docetaxel: a member of the taxane group of antimitotic chemotherapy medications whose mode of action is to bind and stabilize microtubules and thus disrupt cell division.
dominant gene: the allele that causes a phenotype that is seen in a heterozygous genotype.
donor-cell chimerism analysis: a test that determines the ratio of recipient-to-donor hematopoietic stem cells to monitor the engraftment of donor cells after allogenic hematopoietic stem-cell transplantation.
double-strand break repair: any of several DNA repair processes
used by organisms to repair breaks in DNA that span both strands of DNA at a single location.
DPD (dihydropyrimidine dehydrogenase): the first and rate-limiting enzyme in the catabolism of fluorouracil. When DPD levels in the liver are low, fluorouracil clearance cannot occur in patients receiving fluorouracil-based therapy. DPD deficiency increases the area under the curve of the blood concentration of fluorouracil, thus increasing drug toxicity, which often becomes lethal if used at conventional doses.
DR4: also known as TRAIL-R1, a receptor for TRAIL. See TRAIL (TNF-related apoptosis-inducing ligand).
DR5: also known as TRAIL-R2, a receptor for TRAIL. See TRAIL (TNF-related apoptosis-inducing ligand).
driver mutations: mutations that are causally implicated in oncogenesis or tumor survival. Such mutations have been positively selected during carcinogenesis and often show a recurrent pattern within or across tumor types. This is in contrast with passenger events, which arise from the background mutation rate and do not contribute to oncogenesis.
drug-eluting microsphere: spherical embolic agent loaded with chemotherapy and used to embolize hepatic malignancies.
druggable aberrations: any actionable aberration that can be targeted by novel therapeutics and thereby change the natural history of the disease.
DTC (disseminated tumor cell): demonstration of isolated tumor cells disseminated in the bone marrow.
dual Src/Abl kinase inhibitor: a tyrosine kinase inhibitor that inhibits the tyrosine kinase activities of Src and Abl.
Durie-Salmon PLUS system: a staging system for multiple myeloma that integrates imaging techniques (magnetic resonance imaging, whole-body computed tomography [CT], and positron emission tomography–CT) into an anatomic and functional approach to myeloma staging.
DUSP1 (dual specificity phosphatase 1): a protein with structural features similar to members of the nonreceptor-type protein-tyrosine phosphatase family. The DUSP1 protein has intrinsic phosphatase activity and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. In addition, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation.
DUSP4 (dual specificity protein phosphatase 4): also known as MKP2, a tumor suppressor gene coding for a protein phosphatase that inactivates MAP kinase in vitro and MAP kinase–dependent gene transcription in vivo.
dynamic contrast-enhanced magnetic resonance imaging: a magnetic resonance imaging acquisition strategy involving multiple scans over a set volume during injection of a magnetic resonance contrast agent.
dynamin: a family of proteins with GTPase activity that plays an essential role in endocytosis by catalyzing the fission of clathrin-coated vesicles from the plasma membrane. When bound to another protein, amphiphysin, dynamin exists in a nonoligomeric state in clathrin-coated pits. When recruited to sites of endocytosis, dynamin redistributes and polymerizes around the vesicle necks forming dynamin rings. Lengthwise conformational changes in the dynamin rings are responsible for springlike changes in the dynamin helix, a process important in vesicle fission.