In:
Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 2_Supplement ( 2016-02-01), p. A26-A26
Abstract:
Germline mutations in the BRCA genes are associated with highly increased risk of breast and ovarian cancers and to a lesser extent to prostate and pancreatic cancers. Great number of mutations with variable impact on cancer risk and progression are known in these genes worldwide. A single founder mutation has been detected in each of the BRCA genes in the Icelandic population, making it feasible to study the influence of a single mutation at a population level. The BRCA2999del5 mutation is more frequent and can be found in approximately 6-7% of female breast cancer patients and 40% of male breast cancer patients in Iceland. The mutation leads to a non-functional protein product and is associated with complex chromosomal changes in tumor tissue. Furthermore, the BRCA2999del5 mutation has been associated with poor prognosis, both in breast and prostate cancers, although mutation carriers seem to differ with respect to age of onset and severity of disease. Dysfunctional telomere maintenance can lead to excessive telomere shortening which causes chromosome instability. It is therefore a driving force behind cancer progression and is considered a hallmark of many human cancers. Telomere shortening has been shown to be an early and a common molecular alteration in epithelial cancers, including breast cancers. Previous results from our laboratory, amongst others, have shown that BRCA2 is associated with telomere protection and maintenance. Telomere dysfunction induced foci (TIFs) formation was detected in cell lines derived from heterozygous BRCA2999del5 mutation carriers1. Telomere length has been proposed as a possible predictive factor for cancer risk for various cancers. In the case of breast cancer and BRCA mutation carriers, the results have been conflicting. The aim of the study was to investigate if telomere length in normal and tumor breast tissue is correlated with breast cancer progression and survival in a well-defined group of BRCA2 mutation carriers and sporadic breast cancer cases. The study group consisted of breast cancer patients carrying the BRCA2999del5 Icelandic founder mutation and sporadic cases, matched with respect to age and year of diagnosis. Tumor and normal adjacent tissue samples from these patients were embedded in paraffin and Quantitative Fluorescence in Situ Hybridization method (Q-FISH) was used to carry out telomere length measurements. Telomeres were visualized using a telomeric sequence-specific fluorescence peptide nucleic acid (PNA) probe. A centromere-specific PNA probe was used as an inner control for hybridization efficiency. The results show a clear difference in telomere length of different cell types in normal breast tissue with inner epithelial cells having shorter telomeres than both myoepithelial cells and fibroblasts. These findings support previously reported data in the literature2. The majority of examined tumors have very short telomeres. In mutation carriers, there are indications that less variable telomere length in normal adjacent tissue is associated with reduced breast cancer specific survival. This seems to be more pronounced in the mutation carrier group compared to the sporadic group. Telomere length in adjacent normal tissue appears to be shorter in cases with luminal type than with basal-like tumors. References: 1. Bodvarsdottir, S. K., Steinarsdottir, M., Bjarnason, H. & Eyfjord, J. E. Dysfunctional telomeres in human BRCA2 mutated breast tumors and cell lines. Mutat. Res. Mol. Mech. Mutagen. 729, 90–99 (2012). 2. Kurabayashi, R. et al. Luminal and cancer cells in the breast show more rapid telomere shortening than myoepithelial cells and fibroblasts. Hum. Pathol. 39, 1647–1655 (2008). Citation Format: Birna Thorvaldsdottir, Beth A. Cimini, Morgan E. Diolaiti, Margret Aradottir, Katrin Olafsdottir, Jon G. Jonasson, Elizabeth H. Blackburn, Jorunn E. Eyfjörd. Telomere length in normal and tumor breast tissue from BRCA2 mutation carriers and sporadic breast cancer cases. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A26.
Type of Medium:
Online Resource
ISSN:
1541-7786
,
1557-3125
DOI:
10.1158/1557-3125.ADVBC15-A26
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2097884-4
SSG:
12
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