Copy number changes in triple-negative breast cancer: New molecular targets.

Plný text abstraktu(odkaz vede na stránky ASCO)

Abstrakt byl publikován rovněž v Supplementu časopisu
J Clin Oncol 31, 2013 (suppl; abstr 1063)

 Abstract:

Background: Triple negative breast cancer (TNBC) is associated with tumor aggressiveness and high recurrence rate. Treatment options are limited due to lack of molecular-genetic markers and targeted therapy. The aim of our research is assessment of copy number changes in TNBC patients and identification of potential markers for personalized therapy. Methods: Fresh-frozen tumor tissues were collected from 148 patients with TNBC stage I-III. Genomes of these samples were profiled by Affymetrix SNP6.0 arrays. Arrays were normalized using R/Bioconductor and GISTIC 2.0 was used to identify copy number changes. Results: TNBC showed a high level of chromosomal instability and heterogeneity. More than 200 significantly altered chromosomal regions (q value < 0.25) were identified with frequency from 7.4 to 48% cases. Amplification of cell proliferation regulators (MYC, FGFR2, cyclins E1 and E2, PIK3CA, NFIB), regulators of vascularization (VEGFA) and epithelial–mesenchymal transition (CAV1 and CAV2) were found with high significance (q value < 0.1). Deletions of CDK regulators CDKN2B and CDKN2A, and tumor suppressors PTEN, RB1, APC and POT1 were also detected with highly significant q value < 0.1. Importantly, novel copy number changes of genes influencing inflammation, expression regulation and chromatin modification, localized on 1q, 7p, 8q, 9p, 17q and 19p, were found in more than 15% of samples. Conclusions: Despite the fact that TNBC is a heterogeneous group, several common copy number changes were identified. Our analysis confirmed copy number changes of important known genes as well as identified novel markers involved mainly in inflammatory and regulatory processes which could be targets of future therapies. Grant: Biomedreg CZ.1.05/2.1.00/01.0030.