large-scale genomic gains
Friday 29 August 2008
Large-Scale Genomic Gains commonly arise from chromosomal nondisjunction or unbalanced translocations, which cause complete or partial chromosomal trisomies, or from amplification events affecting DNA segments of different size.
Numerous examples of large-scale genomic gains are associated with specific types of cancer. Since such aberrations involve multiple genes, the identification of their functionally relevant targets has proved to be difficult.
One way to "filter" the genes within regions of DNA copy-number gain is to identify those that are also altered at the RNA or protein level, assuming that genes whose increased dosage translates into increased expression are most likely to be involved in malignant transformation.
This strategy has uncovered new oncogenes in malignant melanoma (MITF and NEDD9 on bands 3p14.2-p14.1 and 6p25-p24, respectively)58,59 and hepatocellular carcinoma (YAP1 and BIRC2 on bands 11q13 and 11q22, respectively) and has identified candidate breast-cancer genes.