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Published in: Breast Cancer Research and Treatment 3/2012

01-08-2012 | Brief Report

Mutational analysis of telomere genes in BRCA1/2-negative breast cancer families with very short telomeres

Authors: Kira Yanowsky, Alicia Barroso, Ana Osorio, Miguel Urioste, Javier Benitez, Beatriz Martinez-Delgado

Published in: Breast Cancer Research and Treatment | Issue 3/2012

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Abstract

A majority of the familial breast cancer cases are not explained by mutations in the best-known high susceptibility genes BRCA1 and BRCA2. Since there is a link between DNA repair and telomere maintenance mechanisms, we have investigated for the first time the role of telomere genes in breast cancer predisposition. By a combination of DHPLC and direct sequencing, we screened for sequence variation in 14 telomere-related genes which included telomerase and shelterin complexes in index cases from 50 BRCA1/2-negative families previously characterized to have very short telomere length in peripheral blood leukocytes. Clear pathogenic changes were not detected in any of the genes analyzed. Most of the changes were non-coding variants and only nine corresponded to coding variants located in TPP1, TINF2, NHP2, TNKS, and RAD54B genes; although only two corresponded to coding missense changes leading to aminoacid changes in genes NHP2 and RAD54B. However, functional prediction analysis and control population studies of both variants ruled out its possible pathogenic role. Our results discard a major contribution of telomere-specific genes in hereditary breast cancer.
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Metadata
Title
Mutational analysis of telomere genes in BRCA1/2-negative breast cancer families with very short telomeres
Authors
Kira Yanowsky
Alicia Barroso
Ana Osorio
Miguel Urioste
Javier Benitez
Beatriz Martinez-Delgado
Publication date
01-08-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2141-2

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