Gene Amplification and Cancer

Abstract

Several types of alterations in the deoxyribonucleic acid (DNA) of somatic cells can induce phenotypic changes that lead to cancer, and gene amplification is the most frequently observed type of genetic change associated with cancer. The mechanisms of gene amplification are not well understood, but better understanding of the role played by gene amplification in cancer may lead to new cancer biomarkers and improved prognostic and diagnostic indicators of cancer progression.

Keywords: adaptive amplification; comparative genomic hybridization; genetic instability; oncogene; aneuploidy

Figure 2.

(a) Schematic diagram of conventional comparative genomic hybridization (CGH). Tumor DNA (labeled with green fluorochrome) and normal reference DNA (labeled with red fluorochrome) are hybridized to normal human metaphase chromosomes in the presence of Cot‐1 DNA. Amplified regions have higher copy number and higher green fluorescence, and regions with deletions have lower copy number and higher red fluorescence. Regions that stain green and red equally have the same copy number in tumor and normal DNA (red/green ratio equals 1.0). (b) Array CGH. Tumor DNA (labeled with Cy5) and normal reference DNA (labeled with Cy3) are hybridized to arrayed cDNA or BAC probes on a glass slide. The Cy3 and Cy5 fluorescence intensity of each probe on the array is measured and the Cy3/Cy5 fluorescence ratio indicates the relative DNA copy number in normal and tumor DNA. The Cy3 fluorescence image (pseudo‐colored green) and the Cy5 fluorescence image (pseudo‐colored red) are superimposed to show regions of increased DNA copy number (amplification), decreased DNA copy number (deletion) and no change.

Figure 1.

Detection of gene amplification by comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH). (a) Fluorescence images of gene amplification by CGH. Fluorescein isothiocyanate (FITC), tetramethylrhodamine (Rhod.) and 4,6‐diamidino‐2‐phenylindole dihydrochloride (DAPI) images from the same metaphase chromosome spread are shown. Each image was acquired using a charge‐coupled device camera and a fluorescence microscope. The green‐to‐red fluorescence ratios were measured along each chromosome. (b) Detection of 2p24–p24 amplification in neuroblastoma. A neuroblastoma with MYCN amplification shows gain at 2p24–p24. (c) MYCN amplification in neuroblastoma using FISH. MYCN amplification is detected as multiple spots in interphase nuclei with two centromeric spots. Chromosome 2 is identified by the tetramethylrhodamine‐labeled pericentromeric probe, and the MYCN is identified with an FITC‐labeled probe.

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References

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Further Reading

Brodeur GM and Saylors III RL (1991) Neuroblastoma, retinoblastoma, and brain tumors in children. Current Opinion in Oncology 3: 485–496.

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Web Links

Recurrent DNA Sequence Copy Number Losses and Amplifications in Human Neoplasms Evaluated by Comparative Genomic Hybridization. CGH Database at Laboratory of Cytomolecular Genetics, University of Helsinki http://www.helsinki.fi/cmg/cgh_data.html

ATP‐binding cassette, sub‐family B (MDR/TAP), member 1 (ABCB1); Locus ID: 5243. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5243

Carbamoyl‐phosphate synthetase 2, aspartate transcarbamylase and dihydroorotase (CAD); Locus ID: 790. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=790

v‐erb‐b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) (ERBB2); Locus ID: 2064. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2064

v‐myc myelocytomatosis viral oncogene homolog (avian) (MYC); Locus ID: 4609. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4609

v‐myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN); Locus ID: 4613. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4613

ATP‐binding cassette, sub‐family B (MDR/TAP), member 1 (ABCB1); MIM number: 171050. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?171050

Carbamoyl‐phosphate synthetase 2, aspartate transcarbamylase and dihydroorotase (CAD); MIM number: 114010. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?114010

v‐erb‐b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) (ERBB2); MIM number: 164870. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?164870

v‐myc myelocytomatosis viral oncogene homolog (avian) (MYC); MIM number: 190080. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?190080

v‐myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN); MIM number: 164840. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?164840

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Uchida, Kazuhiko(Jan 2006) Gene Amplification and Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006047]