A. Molecular biology terminology

Amplification --the production of many copies of a gene. This process can occur normally in certain phases of development, but is also seen when a gene, such as c-myc, loses its transcriptional controls.

Antisense nucleotides --a DNA or RNA sequence that is complementary to the protein coding sequence of a gene or mRNA. Antisense nucleotides can adhere to a specific coding sequence of DNA or RNA and potentially block transcription or translation. Antisense sequences are also used as molecular probes.

Apoptosis --«programmed cell death,» such as is seen in normal tissue reabsorption during development (e.g., tadpole tails). Apoptotic cells show clumps of intracellular organelles in the absence of associated inflammation or necrosis and are phagocytosed. Apoptosis may be the mechanism by which tumor cell populations are decreased by hormones, cytotoxic chemotherapy, and radiation therapy. Apoptosis is genetically regulated. For example, the p53 tumor suppressor oncogene stimulates apoptosis, but the BCL -2 oncogene inhibits apoptosis, decreases normal cell death, and increases cell populations.

Breakpoint cluster regions (BCRs) --regions in the genome where chromosome translocations are likely to occur, which are often situated close to a proto-oncogene. In chronic myelogenous leukemia (CML), a part of a BCR on chromosome 22 near the sis oncogene is exchanged with a portion of chromosome 9, which contains the abl gene, to form the Philadelphia chromosome. The normal c-abl protein is a membrane tyrosine kinase. Infection with retroviruses containing the new abl-bcr fusion gene from chromosome 22 can cause CML in mice.

CDs --«cluster of differentiation» antigens, which appear on leukocyte surface membranes and change as various leukocyte lines differentiate. The type of leukocyte and the stage of differentiation can be determined using monoclonal antibody assays of these CDs. CDs on malignant leukocytes are useful for diagnosis and prognosis of leukocyte malignancies. See Appendix C-4 C-4.

Codon --an ordered set of three nucleotides that code for an amino acid or termination code during RNA translation.

Complementary RNA and DNA --RNA or DNA sequences whose codon sequences are mirror images of each other. Complementary sequences adhere to each other. A known RNA or DNA can be used as a molecular probe to look for its complement. The degree of adherence is a measure of how closely the complementary nucleotides mirror each other.

Chromosome rearrangements (see Appendix C-3 C-3 for nomenclature)--various inversions, translocations, and additions that can alter the environment of growth-controlling genes and lead to malignancy. A number of these rearrangements are specific for a given type of malignancy.

Cyclins --proteins that trigger the entry of cells into the cell cycle by activating the transcription of c-myc and c-mos oncogene proteins, which stimulate DNA synthesis.

Double minutes (DMs) --small extrachromosomal globs of DNA without a centromere that are seen under the microscope. They often indicate abnormal gene amplification in transformed cells.

DNA --deoxyribonucleic acid.

DNA polymerases --a group of enzymes that joins deoxynucleotides aligned along a complementary DNA sequence. Some of these polymerases are used for DNA replication and others for repair.

Exons --Sequences in a gene that code for polypeptides.

Gene --a DNA sequence that codes for a single type of polypeptide. Normal cell genes contain subsequences («introns») scattered through the main sequence that are not used for making polypeptides.

Heterogeneous nuclear RNA sequences --a mixture of nuclear RNA sequences of different sizes. Most of this RNA consists of primary RNA transcripts in the process of rapidly losing their introns to form mRNA.

Homologous sequences --segments of different RNA or DNA nucleotides with the same or complementary nucleotide sequences.

Hybridoma --a hybrid cell that makes a specific monoclonal antibody. The hybrid cells are made from normal mouse lymphocytes that produce antibodies and immortalized mouse plasmacytoma cells that do not make antibodies. The lymphocytes are taken from the spleens of mice exposed to foreign antigens such as human leukocytes. Each splenic lymphocyte makes an antibody to one foreign antigen. These lymphocytes do not replicate, but can survive in a toxic medium (HAT medium). In contrast, the plasmacytoma cells can reproduce but cannot survive in HAT medium. The hybrid cells produce specific antibodies, can reproduce, and can survive in HAT medium, which destroys unhybridized plasmacytoma cells. After the hybrid cells are separated, they are allowed to reproduce several times. This procedure allows the isolation and expansion of clones of cells that produce antibodies to a specific antigen.

Insertional mutagenesis --transformation of a cell by a sequence of viral or cellular DNA, which is inserted into the normal host genome. Inserted sequences that cause transformation may be promoters that deregulate normal genes, or may be cellular proto-oncogenes or viral pro-oncogenes that produce growth control substances. The inserted DNA can also disrupt or combine with normal gene sequences, which then produce abnormal polypeptides. LTRs (see retrovirus terminology) are powerful promoters and can cause abnormal activation of nearby control genes that control normal growth.

Introns --noncoding gene sequences. After a gene is transcribed into RNA, the corresponding RNA intron folds back on itself to form loops, or «lariats,» that are removed, degraded, and not used for translation of mRNA into protein. Introns appear to regulate transcription and shuffle nucleotide sequences around to produce new proteins and genetic diversity. Introns are present in normal cells but are absent in oncogenic retroviruses.

Kinases --enzymes that regulate a variety of proteins and nucleotides by phosphorylation.

Messenger RNA (mRNA) --RNA with all introns removed and ready to be translated into protein.

Mis-sense sequences --DNA sequences with sections of abnormal codons, whose protein products function abnormally or not at all.

Monoclonal antibody --an antibody made by hybridoma cell cultures that is highly specific for a specific cell surface antigen.

Nucleosides --a purine or pyrimidine base combined with a sugar (i.e., ribose or deoxyribose for RNA or DNA).

Nucleotides --a nucleoside joined with a phosphate group.

Oncogene --a gene that can cause cells to manifest a malignant phenotype.

Polymerase chain reaction (PCR) --a technique for expanding the amount of very small sequences of DNA.

Promoter --a sequence of DNA near a particular gene that initiates the transcription of that gene.

Proto-oncogenes --normal cell genes that are homologous to viral oncogenes (v-onc) or cellular oncogenes (c-onc) and which typically code for proteins that are essential for control of proliferation and differentiation. Their names are written in italics and begin with a c-plus a three letter symbol for the particular gene (e.g., c-mos).

RNA --ribonucleic acid.

Signal transduction --the mechanism by which extracellular molecules affect intracellular chemistry and biology. Signal transduction is essential for growth and differentiation in multicellular organisms.

Transcription --the production of a complementary (mirror image) RNA sequence from a DNA template.

Transcription factors --specific proteins that bind to control elements of genes. Families of transcription factors include helix-loop-helix proteins, helix-turn-helix proteins and leucine zipper proteins.

Transfection --The introduction of DNA sequences from one cell into the genome of another. Several cellular oncogenes (c-onc) were discovered by transfecting normal cells with DNA taken from cancer cells. After several generations of transformed daughter cells, all of the transfected DNA is lost except the c-onc.

Translation --the production of proteins by ribosomes from mRNA in the cell cytoplasm.

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