N-acetyltransferase: enzymes expressed from the genes NAT1 and NAT2. Both enzymes are capable of N-acetylation and O-acetylation, as well as N, O-acetylation reactions, which have implications in the detoxification of carcinogens. Allelic variations of the genes exist, but their significance has yet to be fully characterized.
nanomedicine: the application of nanotechnology to medicine, including the use of nanomaterials for drug delivery to tumors and nanoelectronic biosensors. Delivery of effective amounts of drugs with current nanomedicine remains a challenge for this field. One nanometer is one millionth of a millimeter.
National Cancer Data Base (NCDB): clinical oncology database in the United States that is jointly sponsored by the American College of Surgeons and the American Cancer Society and sourced from hospital cancer registry data. National Cancer Data Base data are used to analyze and track patients with malignant diseases, their treatments, and their outcomes.
natural killer cells (NK cells): cells that belong to the innate immune system and are specialized to kill target cells that are either infected with viruses or host cells that have become cancerous. CD56 is a surface marker specific to NK cells.
N-CoR (nuclear receptor co-repressor): a transcriptional co-repressor.
nearest-neighbor classification: classification of a patient specimen on the basis of the genes selected as being differentially expressed between the diagnostic or prognostic classes. The vector of expression levels (ie, the expression profile) for the specimen to be classified is compared with each expression profile for a training set of specimens on the basis of a defined distance function between pairs of profiles. The distance function uses only those selected genes. The specimen to be classified is predicted to be in the same class as that in the training set to which it is closest.
negative predictive value: the probability of a negative test result
being truly negative.
neoadjuvant therapy: the administration of chemotherapy prior to surgery. Induction chemotherapy is generally designed to decrease the size of the tumor prior to resection and to increase the rate of complete (R0) resections.
neobladder: a form of urinary diversion where a segment of intestine (typically ileum) is separated and folded to form a pouch that can hold urine. The ureters are anastomosed to this pouch and the pouch is anastomosed to the urethra. This enables the patient to void through the urethra.
nephrectomy: the surgical removal of a kidney. Radical nephrectomy includes removing the entire kidney and its surrounding fatty tissue. A partial nephrectomy includes removal of only part of the kidney that encompasses the diseased area/tumor.
neratinib (HKI-272): a small molecule, irreversible pan-tyrosine kinase inhibitor that inhibits human epidermal growth factor receptor (HER) 1, HER2, and HER4 developed by Puma Biotechnology (Los Angeles, CA) and evaluated in clinical trials in patients with HER2-positive breast cancer and solid tumors with a HER2 mutation.
neuraminidase: catalyzers of the a-glycosidic cleavage of terminal N-acetyl neuraminic acid (also called sialic acid) from sialylated glycoconjugates. Widely present in viruses, bacteria, fungi, protozoa, birds, and mammals, this family of hydrolases shares a conserved active site and similar sequence motifs. In mammals, three types of neuraminidase are defined on the basis of their cellular location (ie, lysosomal, plasma membrane, and cytosolic), which may determine their biochemical properties. In viruses, for example, neuraminidase is a glycoprotein on the surface of the influenza virus that destroys the infected cells receptor for viral hemagglutinin.
neutralizing antibody: antibody produced by the patient that
abrogates the cytotoxicity of the immunotoxin.
neutropenic fever: an oral temperature of at least 100.4°F for at least 1 hour when the absolute neutrophil count is < 0.5 × 109/L.
neutrophils: the most abundant of the white blood cells in the peripheral circulation. The cell is a part of the innate immune system and is important in clearing bacterial infections. It also plays a part in chronic infections, has been observed intratumorally in many cancers,
and may play a role in the initiation and progression of cancer. Immunohistochemical markers of neutrophils comprise, among others,
CD66B+ and elastase.
next-generation sequencing (NGS): modern sequencing technologies that have enabled very efficient parallel sequencing of thousands and millions of DNA/RNA fragments in a matter of hours or days. While these modern sequencing technologies are usually applied to query smaller stretches of DNA/RNA than what is obtained by Sanger sequencing, the ability to sequence much more quickly and cheaply has revolutionized the application of sequencing in cancer biology.
NextGen Sequencing: a non-Sanger rapid DNA sequencing method that can be done with greater speed, developed after the first methodologic articles describing relatively rapid DNA sequencing produced by Sanger et al (1977).
NF1**: gene coding for the protein neurofibromin, which is a tumor suppressor protein and negative regulator of the RAS signal transduction pathway.
NF1* (neurofibromatosis type 1): a dominant hereditary disease caused by germline mutation of the NF1** gene; also known as von Recklinghausens
NF-κB (nuclear factor kappa B): a transcriptional factor involved in the transcriptional activation of genes that regulate different cellular processes. The nuclear location of NF-κB is restricted by its interaction with an inhibitor, I-κ B, which sequesters it in the cytoplasm. When I-κ B is phosphorylated and degraded in response to different stimuli, NF-κB becomes free to enter the nucleus.
NG2: a membrane-spanning protein that is expressed by cells in several different developmental lineages, including oligodendrocyte progenitors, chondroblasts, and pericytes/smooth muscle cells.
Nijmegen breakage syndrome (NBS): an autosomal recessive, chromosomal instability syndrome characterized by short stature, microcephaly, ovarian failure in females, and immunodeficiency. NBS is also associated with an increased risk of cancer, particularly lymphoma. The NBS1 gene encodes a protein that is involved in the repair of double strand breaks in DNA. Homozygous carriers of mutant NBS1 alleles develop NBS.
nitric oxide (NO): synthesized within cells by NO synthase. NO relaxes smooth muscles and has been implicated almost universally in the functioning of a variety of cellular processes.
NKT cells: natural killer cells distinct from T cells or NK cells. NKT cells are CD4+ T cells, which express some cell surface markers that are specific of NK cells.
NNRTI (non-nucleoside reverse transcriptase inhibitor): inhibitors that inhibit HIV reverse transcriptase and decrease viral loads.
nomogram: a prediction tool based on the Cox proportional hazards regression model that incorporates factors included in any staging system. It can also add other clinical and pathologic factors known to have an impact on outcome.
non-CSD melanoma: melanomas without marked solar elastosis of the surrounding dermis.
noninferiority clinical trial: a clinical trial that aims to demonstrate that the outcome is not worse than the standard or comparator by more than a prespecificed amount.
nonrandom X-chromosome inactivation (HUMARA assay): a common assay that detects X-xhromosome inactivation by examining inactivation of the human androgen receptor (HUMARA) on the X-chromosome.
Tumors arise from a single genetically altered cell. Consequently, detection of monoclonality, a genetic similarity among the cells in a tumor mass, can be used to distinguish neoplastic from polyclonal or hyperplastic lesions. Clonality can be established based on X-chromosome inactivation analysis. During early embryonic development of mammalian female embryos, one of the two X-chromosomes in each cell is randomly deactivated by the methylation of deoxycytosine residues. Once established, genetic imprinting retains X-chromosome inactivation through all subsequent cell divisions. The cells in a clonal tumor all show inactivation of the same copy of the X-chromosome.
nonreceptor tyrosine kinases: cellular tyrosine kinases that are not membrane-spanning tyrosine kinases receptors.
nonseminoma: a type of cancer that begins in cells that form sperm or eggs. There are several types of nonseminoma tumors, including embryonal carcinoma, malignant teratoma, choriocarcinoma, and yolk sac tumor. These tumors are usually made up of more than one type of cancer cell. Although nonseminomas occur most often in the testicles or ovaries, they can occur in other tissues, such as the brain, chest, or abdomen. This happens when cells that have the ability to form sperm or eggs are found in other parts of the body.
nonsense: a mutation that changes a codon that codes for an amino acid into a stop codon, therefore terminating translation.
nonsense mutation: a mutation that changes a codon that codes for an amino acid into a stop codon, therefore terminating translation.
nonsentinel lymph node: lymph nodes harvested after the completion lymph node dissection performed in patients with sentinel lymph nodepositive melanoma.
non–small-cell lung cancer (NSCLC): a type of lung cancer that includes squamous cell carcinoma, adenocarcinoma,
and large-cell carcinoma.
northern blot analysis: a technique used to determine the presence and abundance of mRNA present in a biologic sample that has been enriched for mRNA.
NOS (nitric oxide synthase): a group of enzymes that is responsible for the synthesis of nitroc oxide from L-arginine and molecular oxygen. Three classes of NOS have been defined: neuronal NOS (commonly called nNOS), inducible NOS (commonly called iNOS), and endothelial NOS (commonly called eNOS). nNOS is active in neuronal tissue and is also responsible for cell communication. iNOS is found in the immune system, and eNOS is found in blood vessels and regulates vascular function.
Noxa: a proapoptotic member of the Bcl-2 family, which contains the Bcl-2 homology 3 (BH3) region but lacks
other BH domains. Noxa functions as an early response gene and a mediator of p53-induced apoptosis. In human cells, Noxa is also designated as PMA-induced protein 1 or APR.
NPD009: another name for the gene encoding 4-aminobutyrate aminotransferase (ABAT).
NPM1: gene coding for nucleophosmin (also called nucleolar phosphoprotein B23 [numatrin]), which is primarily localized in the nucleolus of the nucleus. It contains an N-terminus oligomerization domain, a metal-binding site, two acid-rich domains, and two nuclear localization signals in the C-terminus of the protein. It is an RNA-binding phosphoprotein involved in the assembly of ribosomal proteins into ribosomes and the transport of ribonucleoproteins between the cellular compartments. The gene is involved in several tumor-associated chromosome translocations.
N-RAS: an isoform of RAS. See RAS.
NRP-1 (neuropilin 1): a co-receptor for the vascular endothelial growth factor (VEGF), but distinct from the tyrosine kinase VEGF receptor (VEGFR) family of receptors. NRP-1 augments the binding affinity of the ligand for the tyrosine kinase VEGFR. It is also present on tumor cells and may function independent of the other VEGFRs. It was initially discovered as a neuronal repulsion factor involved in embryologic neuronal guidance.
NRTI (nucleoside/nucleotide reverse transcriptase inhibitor): analogs of nucleosides/nucleotides that are building blocks necessary for DNA synthesis. They inhibit the reverse transcriptase enzyme of HIV, thus inhibiting its replication and leading to decreased viral loads.
nucleosome: the basic level of chromatin organization. Each nucleosome contains 146 base pairs of DNA wrapped around a core of eight histone proteins.
nucleosome remodeling: the reorganization of the functional state of chromatin at the nucleosomal level by an ATP-dependent mobilization of nucleosomes. These alterations are brought about by chromatin remodeling factors and multiprotein complexes containing ATPases of the Swi/Snf subfamily.
nucleotide excision repair (NER): a major DNA repair pathway that repairs primarily bulky DNA adducts caused by environmental mutagens, such as pyrimidine dimers induced by ultraviolet radiation, benzo[a]pyrene-guanine adducts caused by smoking, and
guanine-cisplatinum adducts formed during chemotherapy. In NER, a small region of the strand surrounding the damage is removed from the DNA helix as an oligonucleotide.
null: complete loss of function phenotype. This term is used in reference to the mutation or inactivation of specific genes, resulting in complete absence of protein expression.
null hypothesis: the statistical hypothesis that the observed difference results from chance alone.
NuRD (nucleosome remodeling and deacetylase): a transcriptional repressor complex that includes nuclear remodeling and histone deacetylase activities.
NY-ESO-1: gene coding for antigens recognized on neoplastically transformed cells T cells; also known as CTAG1B or cancer/testis antigen 1B.