Genomic and transcriptional aberrations linked to breast cancer pathophysiologies
Genomic and transcriptional aberrations linked to breast cancer pathophysiologies
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DOI：
10.1016/j.ccr.2006.10.009
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发表时间：
2006-12-01
期刊：
影响因子：
50.3
通讯作者：
Gray, Joe W.
中科院分区：
文献类型：
--
作者：
Chin, Koei;DeVries, Sandy;Gray, Joe W.
本研究探讨基因组拷贝数异常（CNAs）在乳腺癌病理生理学中的作用，通过确定复发性CNAs，基因表达和一组积极治疗的早期乳腺肿瘤的临床结果之间的关联。它表明，复发性CNA在由表达模式定义的肿瘤亚型之间不同，并且根据结果对患者进行分层可以通过测量表达和拷贝数，特别是高水平扩增来改善。66个基因的高水平扩增是潜在的治疗靶点。其中9种（FGFR1、IKBKB、ERBB2、PROCC、ADAM 9、FNTA、ACACA、PNMT和NR1D1）被认为是可药用的。低水平的CNA似乎通过改变RNA和细胞代谢促进癌症进展。
This study explores the roles of genome copy number abnormalities (CNAs) in breast cancer pathophysiology by identifying associations between recurrent CNAs, gene expression, and clinical outcome in a set of aggressively treated early-stage breast tumors. It shows that the recurrent CNAs differ between tumor subtypes defined by expression pattern and that stratification of patients according to outcome can be improved by measuring both expression and copy number, especially high-level amplification. Sixty-six genes deregulated by the high-level amplifications are potential therapeutic targets. Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism.