High-resolution genomic and expression analyses of copy number alterations in breast tumors

摘要: Analysis of recurrent DNA amplification can lead to the identification cancer driver genes, but this process is often hampered by low resolution existing copy number analysis platforms. Fifty-one breast tumors were profiled for alterations (CNAs) with high-resolution Affymetrix 500K SNP array. These also expression-profiled and surveyed mutations in selected genes commonly mutated (TP53, CDKN2A, ERBB2, KRAS, PIK3CA, PTEN). Combined common CNAs revealed putative associations between features. both prevalence amplitude defined regions alteration. Compared previous array comparative genomic hybridization studies, our provided boundaries frequently altered that approximately one-fourth size, greatly reducing potential alteration-driving genes. Expression data from matched tumor samples used further interrogate functional relevance located amplicons. Although support importance some known such as refined amplicon at other locations, 8p11-12 11q13.5-q14.2, reduce indicate alternatives suggested cases. For example, previously reported 17q23.2 reduced a 249 kb minimal region containing RPS6KB1 well oncogenic microRNA mir-21. High-resolution provides insight into many amplicons their relationships gene expression, point subtype classifications. This article contains Supplementary Material available http://www.interscience.wiley.com/jpages/1045-2257/suppmat.