The significance of genomic instability and tumor-associated gene mutations for the prognosis of breast cancer in postmenopausal patients

Authors

• A-S Liegmann
• A Lischka
• JK Habermann
• T Ried
• K Heselmeyer-Haddad

Abstract

Each year 1.5 million women develop breast cancer worldwide, the most frequent cancer with the highest mortality. One difficulty is the estimation of the individual prognosis and choice of therapy due to the inter-tumor and inter-individual heterogeneity. This heterogeneity leads to differences in tumor growth, progression and metastatic potential due to distinct molecular idiosyncrasies. As a result, the prognostic value of current clinical parameters, for example the TNM grading system, is limited. In order to improve individual prognostication, and hence treatment stratification, extended knowledge on alterations of molecular mechanisms as additional predictors of breast cancer is essential. Toward this goal we correlated genomic alterations in tumor-samples from 37 postmenopausal patients (more than 20 years of follow up) with disease free survival times. We performed multicolor-interphase fluorescence-in-situ-hybridization (miFISH) on 20 samples of patients with short survival and on 17 samples of patients with long survival by enumerating copy numbers of the tumor suppressor genes DBC2, CDH1, TP53 and the oncogenes COX2, MYC, HER2, CCND1 and ZNF217. Our results confirmed the presence of both diploid and aneuploid breast cancer. MiFiSH analysis allowed enumeration of copy numbers of relevant oncogenes including high level amplifications of HER2 and MYC with deletion of TP53 in patients with short survival. In addition, targeted sequencing of 563 cancer-related genes (OncoVar panel) will be performed on all samples.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021