Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis.

作者: S S Kwek , R Roy , H Zhou , J Climent , J A Martinez-Climent

DOI: 10.1038/ONC.2009.34

关键词: GeneComparative genomic hybridizationGene duplicationBiologyOncogene Protein p55(v-myc)GeneticsGene dosageAmpliconRegulation of gene expressionCarcinogenesis

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.

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