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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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Autores principales: Martinez-Delgado, Beatriz, Yanowsky, Kira, Inglada-Perez, Lucia, Domingo, Samuel, Urioste, Miguel, Osorio, Ana, Benitez, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145621/
https://www.ncbi.nlm.nih.gov/pubmed/21829373
http://dx.doi.org/10.1371/journal.pgen.1002182
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author Martinez-Delgado, Beatriz
Yanowsky, Kira
Inglada-Perez, Lucia
Domingo, Samuel
Urioste, Miguel
Osorio, Ana
Benitez, Javier
author_facet Martinez-Delgado, Beatriz
Yanowsky, Kira
Inglada-Perez, Lucia
Domingo, Samuel
Urioste, Miguel
Osorio, Ana
Benitez, Javier
author_sort Martinez-Delgado, Beatriz
collection PubMed
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.
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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 PLoS Genet 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.
spellingShingle Research Article
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
title 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_short Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
title_sort genetic anticipation is associated with telomere shortening in hereditary breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145621/
https://www.ncbi.nlm.nih.gov/pubmed/21829373
http://dx.doi.org/10.1371/journal.pgen.1002182
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