biostudies-literatureGajduskova PNCI NIH HHSR120https://www.ebi.ac.uk/biostudies/studies/S-EPMC2394771biostudies-literatureUnknown8(6)<h4>Background</h4>Amplifications, regions of focal high-level copy number change, lead to overexpression of oncogenes or drug resistance genes in tumors. Their presence is often associated with poor prognosis; however, the use of amplification as a mechanism for overexpression of a particular gene in tumors varies. To investigate the influence of genome position on propensity to amplify, we integrated a mutant form of the gene encoding dihydrofolate reductase into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells.<h4>Results</h4>We observed site-specific differences in methotrexate sensitivity, amplicon organization and amplification frequency. One site was uniquely associated with a signifiGenome biologyGenome position and gene amplification.PMC2394771R33 CA094407CA90421CA94407R01 CA090421Tokuyasu TGajduskova PKwek SRoydasgupta RPinkel DFridlyand JSnijders AMAlbertson DGfalseGenome position and gene amplification.<h4>Background</h4>Amplifications, regions of focal high-level copy number change, lead to overexpression of oncogenes or drug resistance genes in tumors. Their presence is often associated with poor prognosis; however, the use of amplification as a mechanism for overexpression of a particular gene in tumors varies. To investigate the influence of genome position on propensity to amplify, we integrated a mutant form of the gene encoding dihydrofolate reductase into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells.<h4>Results</h4>We observed site-specific differences in methotrexate sensitivity, amplicon organization and amplification frequency. One site was uniquely associated with a signifi2007-01-01T00:00:00Z20072026-04-30T14:57:44.364Z2026-04-07T16:04:47.253ZS-EPMC23947711758493410.1186/gb-2007-8-6-r120