Adenomatous polyp: A benign tumor of epithelial origin that has the potential to become a carcinoma. Adenomas are often polypoid. A polyp is a growth that protrudes from a mucous membrane; most are benign, but some polyps can become malignant.
Ames assay: An assay system devised by Dr Bruce Ames that uses specially designed Salmonella typhimurium to detect mutagens. Most carcinogens are mutagens, but if mutagenicity of a chemical is detected, ideally new chemical compounds should be tested for carcinogenicity by animal testing.
Aneuploidy: Refers to any condition in which the chromosome number of a cell is not an exact multiple of the basic haploid number. Aneuploidy is found in many tumor cells and may play a fundamental role in the development of cancer.
Angiogenesis: The formation of new blood vessels. Angiogenesis is often active around tumor cells, ensuring that they obtain an adequate blood supply. A number of growth factors are secreted by tumor and surrounding cells (eg, vascular endothelial growth factor, or VEGF) and are involved in this process.
Apoptosis: Cell death due to activation of a genetic program that causes fragmentation of cellular DNA and other changes. Caspases play a central role in the process. Many positive and negative regulators affect it. The protein p53 induces apoptosis as a response to cell DNA damage. Most cancer cells exhibit abnormalities of apoptosis, due to various mutations that help to ensure their prolonged survival.
Benign tumor: A mass of abnormal proliferating cells whose growth is driven by mutations in at least one tumor suppressor or oncogene. These tumor cells are noninvasive and do not metastasize.
Biologic response modifiers: Molecules produced by the body or in the laboratory that when administered to patients alter the body’s response to infection, inflammation and other processes. Examples include monoclonal antibodies, cytokines, interleukins, interferons, and growth factors.
Bloom syndrome: One of the CIN syndromes. Due to mutations in a DNA helicase; subjects are sensitive to DNA damage and may develop various tumors.
Burkitt lymphoma: This is a B cell lymphoma, endemic in parts of Africa, where it mainly affects the jaw and facial bones. It is also found elsewhere. A reciprocal translocation involving the C-MYC gene on chromosome 8 and the immunoglobulin heavy chain gene on chromosome 14 is characteristic.
Cancer: A malignant growth of cells.
Cancer stem cell: A cell within a tumor that has the capacity to self-renew and to give rise to the heterogeneous lineages of cancer cells found in the tumor.
Carcinogen: Any agent (eg, a chemical or radiation) capable of causing cells to become cancerous.
Carcinoma: A malignant growth of epithelial origin. A cancer of glandular origin or showing glandular features is usually designated as an adenocarcinoma.
Caspases: Proteolytic enzymes that play a central role in apoptosis, but are also involved in other processes. Some 15 are present in humans. Caspases hydrolyze peptide bonds just C-terminal to aspartate residues.
Cell cycle: The various events pertaining to cell division, that occurs as a cell goes from one mitosis to another.
Centriole: An array of microtubules that is paired and found in the center of a centrosome. (Also see Centrosome.)
Centromere: The constricted region of a mitotic chromosome where chromatids are joined together. It is in close proximity to the kinetochore. Abnormalities of centromeres may contribute to CI. (Also see Kinetochore.)
Centrosome: A centrally located organelle that is the primary microtubule-organizing center of a cell. It acts as the spindle pole during cell division.
Chromatid: A single chromosome.
Chromatin remodeling: This involves conformational changes of nucleosomes brought about by the actions of multiprotein complexes (such as the SW1/SNF complex). These changes alter gene transcription (turning it on or off, depending on specific conditions). The complexes contain domains homologous to ATP-dependent helicase; these are involved in the changes of conformation. Mutations affecting proteins of the complexes, such as may be found in cancer cells, can affect gene expression. (See also Epigenetics.)
Chromosomal instability (CIN): The rate of gain or loss of whole chromosomes or segments of them caused by abnormalities of chromosome segregation during mitosis. (See also Genome instability and Microsatellite instability.) There are a number of disorders that are named CIN syndromes because they are associated with chromosomal abnormalities. One such is Bloom syndrome, in which a high frequency of sister chromatid exchanges is observed. An increased incidence of various cancers is found in these conditions.
Chromosomal passenger complex: A complex of proteins that plays a key role in regulating mitosis. At the centromere, it directs alignment of the chromosome and participates in spindle assembly. Its proteins include aurora B kinase and survivin. Mutations affecting its proteins may contribute to CI and aneuploidy.
Chromosomal translocation: When part of one chromosome becomes fused to another, often causing activation of a gene at the site. The Philadelphia chromosome (see below) is one of many examples of a chromosomal translocation involved in the causation of cancer.
Clone: All the cells of a clone are derived from one parent cell.
Copy number variations (CNVs): Variations (because of duplications or deletions) among individuals as to the number of copies they have of particular genes. CNVs are being increasingly recognized for various genes, and some may be associated with various diseases, including certain types of cancer.
Driver mutation: A mutation in a gene that either helps cause cancer or accelerates it. Mutations found in tumors that do not cause cancer or its progression are called passenger mutations.
Epigenetic: Refers to changes of gene expression without change of the sequence of bases in DNA. Factors causing epigenetic changes include methylation of bases in DNA, posttranslational modifications of histones and chromatin remodeling.
FAS receptor: A receptor that initiates apoptosis when it binds its ligand, FAS. FAS is a protein present on the surface of activated natural killer cells, cytotoxic T lymphocytes and other sources.
Gatekeeper: A mutated version of a gene that initiates the cascade of events that cause oncogenesis (eg, RB).
Genome instability: This refers to a number of alterations of the genome, of which the two principal ones are CIN and microsatellite instability. In general, it reflects the fact that the genomes of cancer cells are more susceptible to mutations than are normal cells, in part due to impairment of DNA repair systems.
Growth factors: A variety of polypeptides secreted by many normal and tumor cells. These molecules act via autocrine (affects the cells that produce the growth factor), paracrine (affects neighboring cells) or endocrine (travels in the blood to affect distant cells) modes. They stimulate proliferation of target cells via interactions with specific receptors. They also have many other biologic properties.
Hypoxia-inducible factors (HIFs): A family of transcription factors (at least three) important in directing cellular responses to varying levels of oxygen. Each factor is made up of a different oxygen-regulated α-subunit and a common constitutive β-subunit. At physiological levels of oxygen, the α-subunit undergoes rapid degradation, initiated by prolyl hydroxylases. HIFs have various functions; eg, HIF-1 up-regulates various genes encoding enzymes of glycolysis, and also the expression of vascular endothelial growth factor (VEGF).
Kinetochore: A structure that forms on each mitotic chromosome adjacent to the centromere. Mutations affecting the structures of its component proteins could contribute to causing CI. (See also Centromere.)
Leukemias: A variety of malignant diseases in which various white cells (eg, myeloblasts, lymphoblasts, etc) proliferate in an unrestrained manner. Leukemias may be acute or chronic.
Loss of heterozygosity (LOH): This occurs when there is loss of the normal allele (often encoding a tumor suppressor gene) from a pair of heterozygous chromosomes, allowing the results of the defective allele to be manifest clinically.
Lymphoma: A group of neoplasms arising in the reticuloendothelial and lymphatic systems. Major members of the group are Hodgkin and non-Hodgkin lymphomas.
Malignant cells: They are cancer cells—cells with the ability to grow in an unrestrained manner, to invade, and to spread (metastasize) to other parts of the body.
Metastasis: The ability of cancer cells to spread to distant parts of the body and grow there.
Microsatellite instability: Expansion or contraction of short tandem repeats (microsatellites) due to replication slippage, abnormalities of mismatch repair or of homologous recombination. For Microsatellites, see Chapter 35.
Nanotechnology: The development and application of devices that are only a few nanometers in size. (10−9 m equals = 1 nm). Some are being applied to cancer therapy. For example, nanoshells (very small spherical particles with a silica core and a gold covering) tuned to near-infrared light have been administered to mice with tumors, in which the nanoshells accumulate. The tumors were subsequently subjected to near infrared laser light. This heated the tumors selectively, killed them, and there was no sign of recurrence on follow-up. (Morton JG, et al: Nanoshells for photothermal cancer therapy. Methods Mol Biol 2010;624:101. June 25, 2010.)
Necrosis: Cell death induced by chemicals or tissue injury. Various hydrolytic enzymes are released and digest cellular molecules. It is not a genetically programmed process, as is apoptosis. Affected cells usually burst and release their contents, causing local inflammation.
Neoplasm: Any new growth of tissue, benign or malignant.
Oncogene: A mutated proto-oncogene whose protein product is involved in the transformation of a normal cell to a cancer cell.
Oncology: The area of medical science that concerns itself with all aspects of cancer (causes, diagnosis, treatment, etc).
Philadelphia chromosome: A chromosome formed by a reciprocal translocation between chromosomes 9 and 22. It is the cause of chronic myeloid leukemia (CML). To form the abnormal chromosome, part of the BCR (breakpoint cluster region) gene of chromosome 22 fuses with part of the ABL gene (encodes a tyrosine kinase) of chromosome 9, directing the synthesis of a chimeric protein that has unregulated tyrosine kinase activity and drives cell proliferation. The activity of this kinase is inhibited by the drug Imatinib (Gleevec), which has been successfully used to treat CML. (See also Chromosomal translocation.)
Procarcinogen: A chemical that becomes a carcinogen when altered by metabolism.
Proto-oncogene: A normal cellular gene, which when mutated can give rise to a product that stimulates the growth of cells, contributing to the development of cancer.
Replication slippage: A process in which, because of misalignment of DNA strands where repeat sequences occur, DNA polymerase pauses and dissociates, resulting in deletions or insertions of repeat sequences.
Retinoblastoma: A rare tumor of the retina. Mutation of the RB tumor suppressor gene plays a key role in its development. Patients with hereditary retinoblastomas have inherited one mutated copy of the RB gene, and need only one further mutation to develop the tumor. Patients with sporadic retinoblastomas are born with two normal copies, and require two mutations to inactivate the gene.
Rous sarcoma virus (RSV): An RNA tumor virus that causes sarcomas in chickens. It was discovered in 1911 by Peyton Rous. It is a retrovirus, using reverse transcriptase in its replication; the DNA copy of its genome subsequently integrates into the host cell genome. It has been widely used in studies of cancer, and its use has led to many important findings.
Sarcoma: A malignant tumor of mesenchymal origin (eg, from cells of the extracellular matrix or other sources).
Telomeres: Structures at the ends of chromosome that contain multiple repeats of specific hexanucleotide DNA sequences. The telomeres of normal cells shorten on repeated cell division, which may result in cell death. The enzyme telomerase replicates telomeres and is often expressed in cancer cells, helping them to evade cell death. Telomerase is usually not detected in normal somatic cells.
Translocation: The displacement of one part of a chromosome to a different chromosome or to a different part of the same chromosome. Classic examples are the translocation found in Burkitt lymphoma (see above) and the translocation between chromosomes 9 and 22, which causes the appearance of the Philadelphia chromosome found in chronic myelogenous leukemia. Translocations have been found in many cancer cells.
Transformation: The process by which normal cells in tissue culture become changed to abnormal cells (eg, by oncogenic viruses or chemicals), some of which may be malignant.
Tumor: Any new growth of tissue, but usually refers to a benign or malignant neoplasm.
Tumor suppressor gene: A gene whose protein product normally restrains cell growth, but when its activity is lost or reduced by mutation contributes to the development of a cancer cell.