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Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes Export

Molecular Cancer Research, Vol. 7, No. 4. (April 2009), pp. 511-522.

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breast_cancer copy-number subtypes

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10.1158/1541-7786.MCR-08-0107 Breast cancers can be divided into subtypes with important implications for prognosis and treatment. We set out to characterize the genetic alterations observed in different breast cancer subtypes and to identify specific candidate genes and pathways associated with subtype biology. mRNA expression levels of estrogen receptor, progesterone receptor, and HER2 were shown to predict marker status determined by immunohistochemistry and to be effective at assigning samples to subtypes. HER2 cancers were shown to have the greatest frequency of high-level amplification (independent of the amplicon itself), but triple-negative cancers had the highest overall frequencies of copy gain. Triple-negative cancers also were shown to have more frequent loss of phosphatase and tensin homologue and mutation of which may contribute to genomic instability. We identified and validated seven regions of copy number alteration associated with different subtypes, and used integrative bioinformatics analysis to identify candidate oncogenes and tumor suppressors, including , and . We tested the candidate oncogene and showed that it enhances the anchorage-independent growth of breast cancer cells. The genome-wide and region-specific differences between subtypes suggest the differential activation of oncogenic pathways. (Mol Cancer Res 2009;7(4):511â22)


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