Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer

There is increasing evidence suggesting that short telomeres and subsequent genomic instability contribute to malignant transformation. Telomere shortening has been described as a mechanism to explain genetic anticipation in dyskeratosis congenita and Li-Fraumeni syndrome. Since genetic anticipation...

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Main Authors:	Martinez-Delgado, Beatriz, Yanowsky, Kira, Inglada-Perez, Lucia, Domingo, Samuel, Urioste, Miguel, Osorio, Ana, Benitez, Javier
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145621/

id	pubmed-3145621
recordtype	oai_dc
spelling	pubmed-31456212011-08-09 Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer Martinez-Delgado, Beatriz Yanowsky, Kira Inglada-Perez, Lucia Domingo, Samuel Urioste, Miguel Osorio, Ana Benitez, Javier Research Article There is increasing evidence suggesting that short telomeres and subsequent genomic instability contribute to malignant transformation. Telomere shortening has been described as a mechanism to explain genetic anticipation in dyskeratosis congenita and Li-Fraumeni syndrome. Since genetic anticipation has been observed in familial breast cancer, we aimed to study telomere length in familial breast cancer patients and hypothesized that genetic defects causing this disease would affect telomere maintenance resulting in shortened telomeres. Here, we first investigated age anticipation in mother-daughter pairs with breast cancer in 623 breast cancer families, classified as BRCA1, BRCA2, and BRCAX. Moreover, we analyzed telomere length in DNA from peripheral blood leukocytes by quantitative PCR in a set of 198 hereditary breast cancer patients, and compared them with 267 control samples and 71 sporadic breast cancer patients. Changes in telomere length in mother-daughter pairs from breast cancer families and controls were also evaluated to address differences through generations. We demonstrated that short telomeres characterize hereditary but not sporadic breast cancer. We have defined a group of BRCAX families with short telomeres, suggesting that telomere maintenance genes might be susceptibility genes for breast cancer. Significantly, we described that progressive telomere shortening is associated with earlier onset of breast cancer in successive generations of affected families. Our results provide evidence that telomere shortening is associated with earlier age of cancer onset in successive generations, suggesting that it might be a mechanism of genetic anticipation in hereditary breast cancer. Public Library of Science 2011-07-28 /pmc/articles/PMC3145621/ /pubmed/21829373 http://dx.doi.org/10.1371/journal.pgen.1002182 Text en Martinez-Delgado et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Martinez-Delgado, Beatriz Yanowsky, Kira Inglada-Perez, Lucia Domingo, Samuel Urioste, Miguel Osorio, Ana Benitez, Javier
spellingShingle	Martinez-Delgado, Beatriz Yanowsky, Kira Inglada-Perez, Lucia Domingo, Samuel Urioste, Miguel Osorio, Ana Benitez, Javier Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
author_facet	Martinez-Delgado, Beatriz Yanowsky, Kira Inglada-Perez, Lucia Domingo, Samuel Urioste, Miguel Osorio, Ana Benitez, Javier
author_sort	Martinez-Delgado, Beatriz
title	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_short	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_full	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_fullStr	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_full_unstemmed	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_sort	genetic anticipation is associated with telomere shortening in hereditary breast cancer
description	There is increasing evidence suggesting that short telomeres and subsequent genomic instability contribute to malignant transformation. Telomere shortening has been described as a mechanism to explain genetic anticipation in dyskeratosis congenita and Li-Fraumeni syndrome. Since genetic anticipation has been observed in familial breast cancer, we aimed to study telomere length in familial breast cancer patients and hypothesized that genetic defects causing this disease would affect telomere maintenance resulting in shortened telomeres. Here, we first investigated age anticipation in mother-daughter pairs with breast cancer in 623 breast cancer families, classified as BRCA1, BRCA2, and BRCAX. Moreover, we analyzed telomere length in DNA from peripheral blood leukocytes by quantitative PCR in a set of 198 hereditary breast cancer patients, and compared them with 267 control samples and 71 sporadic breast cancer patients. Changes in telomere length in mother-daughter pairs from breast cancer families and controls were also evaluated to address differences through generations. We demonstrated that short telomeres characterize hereditary but not sporadic breast cancer. We have defined a group of BRCAX families with short telomeres, suggesting that telomere maintenance genes might be susceptibility genes for breast cancer. Significantly, we described that progressive telomere shortening is associated with earlier onset of breast cancer in successive generations of affected families. Our results provide evidence that telomere shortening is associated with earlier age of cancer onset in successive generations, suggesting that it might be a mechanism of genetic anticipation in hereditary breast cancer.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145621/
_version_	1611468076069421056

Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer

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