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genic amplification

Sunday 8 May 2005

Gene amplification is a copy number increase of a restricted region of a chromosome arm. It is prevalent in some tumors and is associated with overexpression of the amplified gene(s).

Amplified DNA can be organized as extrachromosomal elements, as repeated units at a single locus or scattered throughout the genome.

Common chromosomal fragile sites, defects in DNA replication or telomere dysfunction might promote amplification.

Some regions of amplification are complex, yet elements of the pattern are reproduced in different tumor types.

A genetic basis for amplification is suggested by its relative frequency in some tumor subtypes, and its occurrence in "early" preneoplastic lesions.

Clinically, amplification has prognostic and diagnostic usefulness, and is a mechanism of acquired drug resistance.

See also

- oncogene amplification

Reviews

- Myllykangas S, Bohling T, Knuutila S. Specificity, selection and significance of gene amplifications in cancer. Semin Cancer Biol. 2007 Feb;17(1):42-55. PMID: 17161620

- Myllykangas S, Himberg J, Bohling T, Nagy B, Hollmen J, Knuutila S. DNA copy number amplification profiling of human neoplasms. Oncogene. 2006 Nov 23;25(55):7324-32. PMID: 16751803

- Myllykangas S, Knuutila S. Manifestation, mechanisms and mysteries of gene amplifications. Cancer Lett. 2006 Jan 28;232(1):79-89. PMID: 16288831

- Albertson DG. Gene amplification in cancer. Trends Genet. 2006 Aug;22(8):447-55. PMID: 16787682

- Claycomb JM, Orr-Weaver TL. Developmental gene amplification: insights into DNA replication and gene expression. Trends Genet. 2005 Mar;21(3):149-62. PMID: 15734574

References

- Bignell GR, Santarius T, Pole JC, Butler AP, Perry J, Pleasance E, Greenman C, Menzies A, Taylor S, Edkins S, Campbell P, Quail M, Plumb B, Matthews L, McLay K, Edwards PA, Rogers J, Wooster R, Futreal PA, Stratton MR. Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 2007 Sep;17(9):1296-303. PMID: 17675364

- Heidenblad M, Lindgren D, Veltman JA, Jonson T, Mahlamaki EH, Gorunova L, van Kessel AG, Schoenmakers EF, Hoglund M. Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: implications for the interpretation of genomic amplifications. Oncogene. 2005 Mar 3;24(10):1794-801. PMID: 15688027