作者: S S Kwek , R Roy , H Zhou , J Climent , J A Martinez-Climent
DOI: 10.1038/ONC.2009.34
关键词: Gene 、 Comparative genomic hybridization 、 Gene duplication 、 Biology 、 Oncogene Protein p55(v-myc) 、 Genetics 、 Gene dosage 、 Amplicon 、 Regulation of gene expression 、 Carcinogenesis
摘要: Co-amplification at chromosomes 8p11-8p12 and 11q12-11q14 occurs often in breast tumors, suggesting possible cooperation between genes these regions oncogenesis. We used high-resolution array comparative genomic hybridization (array CGH) to map the minimal amplified regions. The 8p 11q amplicons are complex consist of least four amplicon cores each site. Candidate oncogenes mapping were identified by combining copy number RNA protein expression analyses. These studies also suggested that CCND1 11q13 induced ZNF703 8p12, which was subsequently shown be mediated Rb/E2F pathway. Nine candidate from 8p12 further evaluated for oncogenic function. None individually promoted colony formation soft agar or collaborated with other functionally. On hand, FGFR1 DDHD2 cooperated functionally MYC, whereas a dominant negative form TP53. observations highlight complexity functional consequences rearrangements occur cancer amplicons, including transcriptional cross-talk as well their major pathways tumorigenesis.