Project description: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 DHFR into different positions in the human genome, challenged cells with methotrexate and then studied the genomic alterations arising in drug resistant cells. We observed site specific differences in methotrexate sensitivity, organization of amplicons and amplification frequency. One site was uniquely associated with a significantly enhanced propensity to amplify and recurrent amplicon boundaries, possibly implicating a rare folate sensitive fragile site in initiating amplification. Hierarchical clustering of gene expression patterns and subsequent gene enrichment analysis revealed two clusters differing significantly in expression of MYC target genes independent of integration site. These studies suggest that genome context together with the particular challenges to genome stability experienced during the progression to cancer contribute to the propensity to amplify a specific oncogene or drug resistance gene, whereas the overall functional response to drug (or other) challenge may be independent of the genomic location of an oncogene. Keywords: Gene amplification, array CGH, chromosomal fragile sites

2007-10-08 | GSE6262 | GEO

Highly sensitive and specific screening of EGFR mutation using a PNA microarray-based fluorometric assay based on rolling circle amplification and graphene oxide.

Project description: Not available

| S-EPMC9075832 | biostudies-literature

Dual-Signal Amplification Strategy for Sensitive MicroRNA Detection Based on Rolling Circle Amplification and Enzymatic Repairing Amplification.

Project description: Not available

| S-EPMC7758957 | biostudies-literature

Genome position and gene amplification.

Project description: Not available

| S-EPMC2394771 | biostudies-literature

Interfacial Effect-Based Quantification of Droplet Isothermal Nucleic Acid Amplification for Bacterial Infection.

Project description: Not available