Genomic andtranscriptional aberrations linked tobreastcancer pathophysiologies

Summary 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 breasttumors. Itshowsthat therecurrent CNAsdiffer betweentumor subtypesdefined by expressionpattern andthat stratificationofpatientsaccordingtooutcomecanbeimprovedbymeasuringbothexpressionandcopynumber,especiallyhighlevel 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.