Glossary
Please Note: This glossary is not comprehensive.
Technology and techniques have been highlighted in blue.
Allelic imbalance (AI): refers to the balance of allelic heterozygosity in the genomic DNA between tumor vs normal. Can be defined as either Loss &/ OR gain depending on the paper.
Codon: triplet of DNA nucleotides coding for amino acids.
Comparative genomic hybridization (CGH) Hybridization between normal genome and tumor genome on metaphase spreads. Direct examination of DNA/karyotypic aberrations in the genomic DNA from tumor and normal cells.
Conformation-sensitive gel electrophoresis (CSGE); is a rapid Gel detection system for single-base differences in double-stranded PCR products and DNA fragments.
Deletion: Absence of a segment of DNA; may be as small as a single base or as large as an entire chromosome (see mutation).
Deoxyribonucleic acid (DNA):
Including:
a) Genomic DNA: DNA found in the nucleus.
b) cDNA (complementary): a representation of the gene without intron sequences. Created from mRNA using RT-PCR.
c) Organelle DNA: organelles such as the mitochondria (mtDNA) carry their own genetic material.
Fluorescent in situ Hybridization (FISH); hybridization system between fluorescently labeled probes (either mRNA or DNA ) and tissue sections. Used in the analysis of copy numbers of the area/gene, expression of multiple genes by DNA and RNA in situ hybridization; or a variation on immunohistochemistry.
Fluid microarrays: a miniaturized flow-through system realizing the microsphere-based massively parallel signature sequencing technique, designed to analyze proteins in a fashion analogous to the array-based format of DNA microarrays.
Gene chips (GC): see microarray.
Heterogeneity: means 'mixture'. For example, in this review we have used the term to describe the apparent lack of relationship in physical staging or molecular changes between different primary foci in the same prostate. That is, the genetic mutations seen in one foci are not necessarily those found another in focus in the same prostate, nor are there changes particular to the same stage of oncogenesis.
ImmunoHistochemistry (IH) and Histochemistry; Tagged Antibodies and stains directly on tissue sections to enable semi-quantitation and examination of localization of proteins, cells morphology, ultrastructure of cells the tissue.
in situ hybridization (ISH) & in situ PCR hybridization: Combination of hybridization techniques using primers/probes for target DNA, RNA or protein on tissue sections. As for CGH, the labeled probes (as desired) are hybridized to deparafinised mounted tissue sections. Where there are only very small amounts to be detected, an additional step of PCR is added to increase the amount and thus the chances of detection.
Loss of heterogeneity (LOH): a term used in familial studies and often interchangeably with allelic imbalance and MSA (or MSI). It refers to a particular locus heterozygous for deleterious mutant allele and a normal allele. A deletion or other mutational event within the normal allele renders the cell either hemizygous (one deleterious allele and one deleted allele) or homozygous (both the same) for for the deleterious allele.
Microarray: There are many microarray variants. In this article we have concentrated on Expression microarrays, that is, those studies which investigated changes in the gene transcription. Expression is examined by measuring the relative amounts of specific mRNA.
Essentially, total RNA is collected from patient sample and labeled (eg fluorescence). These are then 'hybridized' to the array consisting of thousands of probes for the genes of interest. Only those transcripts which match a probe (target sequences which can be cDNA or oligonucleotides) will hybridize, thus the more copies that hybridizes the greater the intensity of the signal. By comparing the intensity of the signal from the hybridized normal tissue RNA (cDNA or cRNA) and probe versus the cancer tissue samples, it is possible to tell whether there is elevated or decreased amounts of specific mRNA in cancerous tissue.
This term is often incorrectly used to indicate.
Fluid microarray
Tissue Microarrays (TMA's).
Protein array
Microsatellite: short repeated nucleotide sequences, generally non-coding.
Microsatellite analysis (MSA) or Microsatellite Instability (MSI): PCR amplification of microsatellite regions of interest within the genome and hybridization techniques Comparison of short non-coding repeats; difference in PCR product band patterns tumor vs normal. Used as markers in allelic and LOH studies.
Mutations: term which covers a variety of types including;
a) insertion, extra genetic material is physically incorporated into the genomic DNA. If this falls within the open reading frame of a gene, this will shift the 'frame' ie the order of nucleotides making up the codons, with serious effects on the gene product. This particular type of insertional mutation is known as a frame shift mutations. Others include duplication mutations.
b) Deletion: genetic material is physically lost/removed, may be as small as a single base or as large as a chromosome. The consequences are more serious where the mutation occurs within coding sequence.
c) Balanced: where genetic material is neither gained or lost; eg a silent base pair change at the 3rd codon position which does not change the coded amino acid.
d) Frame shift; a change (such as an insertion or deletion) within an exon altering the open reading frame (ORF).
Northern Blot (NB): Gel based hybridization technique enabling detection of specific regions of RNA using a labeled probe (a fragment of cRNA usually 200-250bp in length).
Polymerase Chain Reaction (PCR); an amplification technique mimicking the biological process to create copies of DNA (cDNA) using primer pairs (oligonucleotides ranging from 18 nucleotides to 250 nucleotides depending on the system) to 'frame' the region of interest.
Protein arrays; Protein biochips for differential profiling. These are designed to analyze proteins in a fashion analogous to the array-based format of DNA microarrays.
Repair mechanisms: At this time there is believed to be 4 main DNA repair systems:
1) Base excision repair (BER): detects and removes damaged and incorrect bases.
2) Mismatch repair; corrects mistakes during synthesis of new DNA strands.
3) Nucleotide excision repair (NER); repairs and corrects distortion in the helix.
4) Recombinational Repair; repairs DNA crosslinks and double strand breaks.
Restriction Fragment Length Polymorphisms (RFLPs); based on single nucleotide changes. They are generated during SB techniques.
Ribose Nucleic Acids (RNA); ATP, TTP, CTP and UTP (uridine triphosphate); inherently unstable compared to DNA. There are several types of eukaryotic RNA including:
cRNA: complementary RNA; this is created from cDNA in a process which mimics the natural machinery utilizing reverse transcriptase PCR technology.
mRNA: messenger RNA. Also called DNA transcripts, they are the RNA copies of DNA sequence.
rRNA: ribosomal RNA, a number of types which combined with ribosomal proteins are part of the translational machinery.
tRNA: transfer RNA, part of the translational machinery which translate the mRNA into a protein product. NB: TRNA and tRNA have been incorrectly used at times to indicate the total RNA which is present in the cells.
Reverse Transcriptase-PCR (RTPCR); hybridization and amplification technique converting total and/or mRNA into cDNA. A further variation on this technique can then convert the cDNA into cRNA.
Southern Blot, (SB); Gel based hybridization technique enabling detection of a specific region of DNA using a labeled probe (a fragment of DNA usually 200-250bp in length).
Tissue Microarrays (TMA); relocation of multiple tissue samples from conventional histological paraffin blocks to a recipient slide or 'array'. This technique allows for large-scale, parallel in situ analysis of genetic alterations (DNA, RNA or protein). The probes are hybridized to the sample array using techniques such as in situ hybridization, on hundreds of tumor specimens at a time.
Transcription: synthesis of mRNA from DNA template. This can also be referred to as 'gene expression'.
Translation: process of synthesizing protein from mRNA template.
Trisomy: an aberration where 3 copies of an autosomal chromosome are present.
Western blots (WB); gel based hybridisation technique enabling protein detection.
Infrastructure and Technology overview
Literature Selection criteria
Glossary
References
Figure 1: Chromosomal hot spots
Master Table 1a: Review Profile
