Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer
Publication Date
July 28, 2011
Journal
PLOS Genetics
Authors
Beatriz Martinez Delgado, Kira Yanowsky, Lucia Inglada Perez, Samuel Domingo, et al
Volume
7
Issue
7
Pages
e1002182
DOI
https://dx.plos.org/10.1371/journal.pgen.1002182
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002182
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21829373
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145621
Europe PMC
http://europepmc.org/abstract/MED/21829373
Web of Science
000293338600031
Scopus
79960957245
Mendeley
http://www.mendeley.com/research/genetic-anticipation-associated-telomere-shortening-hereditary-breast-cancer
Events
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Mendeley | Further Information

{"title"=>"Genetic anticipation is associated with Telomere shortening in hereditary breast cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Beatriz", "last_name"=>"Martinez-Delgado", "scopus_author_id"=>"6701384111"}, {"first_name"=>"Kira", "last_name"=>"Yanowsky", "scopus_author_id"=>"48762335800"}, {"first_name"=>"Lucia", "last_name"=>"Inglada-Perez", "scopus_author_id"=>"35078660900"}, {"first_name"=>"Samuel", "last_name"=>"Domingo", "scopus_author_id"=>"48761249400"}, {"first_name"=>"Miguel", "last_name"=>"Urioste", "scopus_author_id"=>"7003511749"}, {"first_name"=>"Ana", "last_name"=>"Osorio", "scopus_author_id"=>"7006178585"}, {"first_name"=>"Javier", "last_name"=>"Benitez", "scopus_author_id"=>"7203010415"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"362246875", "sgr"=>"79960957245", "issn"=>"15537390", "pmid"=>"21829373", "scopus"=>"2-s2.0-79960957245", "doi"=>"10.1371/journal.pgen.1002182", "isbn"=>"1553-7390"}, "id"=>"fc3d36f3-022d-3326-8f35-72035066c578", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/genetic-anticipation-associated-telomere-shortening-hereditary-breast-cancer", "reader_count"=>75, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Student > Doctoral Student"=>4, "Researcher"=>19, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>4, "Student > Master"=>8, "Other"=>1, "Student > Bachelor"=>15, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Student > Doctoral Student"=>4, "Researcher"=>19, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>4, "Student > Master"=>8, "Other"=>1, "Student > Bachelor"=>15, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Medicine and Dentistry"=>26, "Agricultural and Biological Sciences"=>29, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>26}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Brazil"=>1, "United Kingdom"=>1, "Australia"=>1}, "group_count"=>2}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/750921"], "description"=>"<p>First quartile (Q1), characterized by the shortest telomeres, was significantly increased in the three hereditary groups, but decrease in the sporadic breast cancer. For analysis of differences in the proportion of cases in Q1 in breast cancer groups and controls, Chi-square test two-sided was performed.</p>", "links"=>[], "tags"=>["hereditary", "sporadic", "cancer", "cases", "quartiles", "telomere"], "article_id"=>421281, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g005", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_hereditary_and_sporadic_breast_cancer_cases_by_quartiles_of_telomere_length_/421281", "title"=>"Distribution of hereditary and sporadic breast cancer cases by quartiles of telomere length.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:11:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/751262"], "description"=>"<p>Data from the mother-daughter pairs with familial breast cancer showing the age of breast cancer diagnosis and the age-adjusted telomere length.</p><p>BR: Breast cancer, BR Bi: Bilateral Breast cancer, OV: Ovarian cancer, Leu: Leukemia, Mel: Melanoma</p>a<p>Families not showing anticipation in the age of onset.</p>", "links"=>[], "tags"=>["telomere", "anticipation", "mother-daughter"], "article_id"=>421634, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.t003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_adjusted_telomere_length_and_anticipation_in_the_age_of_diagnosis_in_mother_daughter_pairs_/421634", "title"=>"Age-adjusted telomere length and anticipation in the age of diagnosis in mother-daughter pairs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 16:16:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/750612"], "description"=>"<p>Kaplan–Meier curves showing the differences in age of onset of familial breast cancer in mothers and daughters in BRCA1 (left panel), BRCA2 (middle panel), and BRCAX (right panel) families. Log-rank test <i>p-</i>values are represented for each group.</p>", "links"=>[], "tags"=>["cancer", "onset", "familial"], "article_id"=>420975, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anticipation_effect_in_the_age_of_breast_cancer_onset_in_the_familial_breast_cancer_genetic_subgroups_/420975", "title"=>"Anticipation effect in the age of breast cancer onset in the familial breast cancer genetic subgroups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:09:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/751144"], "description"=>"<p>(A) Box-plots representing telomere length distribution in mothers and daughters affected with breast cancer, affected mothers and daughters unaffected but carrying <i>BRCA1/2</i> mutations, and control mothers and daughters. Significant differences were found in mother-daughter pairs from familial breast cancer families with a decrease in the telomere length in both affected and unaffected, mutation-carrying daughters, but not in controls. (B) Generational changes in telomere length in mother-daughter pairs with familial breast cancer (n = 19) compared to control mother-daughter pairs (n = 16). Differences between age-adjusted telomere length in daughters and age-adjusted telomere length of the corresponding mother were obtained for affected and control groups. Median value is drawn as a horizontal line for each group. Telomeres of affected daughters were significantly shorter than those of their mothers, compared to the changes observed in control mother-daughter pairs (Mann-Whitney U, p-value = 0.003).</p>", "links"=>[], "tags"=>["telomere", "mother-daughter"], "article_id"=>421517, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_telomere_length_between_mother_daughter_pairs_/421517", "title"=>"Changes in telomere length between mother-daughter pairs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:15:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/750866"], "description"=>"<p>Comparison of age-adjusted telomere length between <i>BRCA1/2</i> mutation carriers (n = 19) and healthy non-carrier sisters (n = 22) from 19 different families (8 BRCA1, 11 BRCA2) is represented through box-plots showing the median and interquartile distance for each group. Age-adjusted telomere length was calculated for each sample as the difference between the actual and the predicted value using the line of best fit from controls (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002182#s4\" target=\"_blank\">Materials and Methods</a>). Atypical (circles) and extreme (asterisks) values are also shown. Mann-Whitney U tests between the groups were performed, and significantly shorter telomeres were found in mutation carriers versus non-carriers. The non-carrier sisters from affected families do not show differences in telomere length with the control women.</p>", "links"=>[], "tags"=>["affected", "mutation", "carriers", "corresponding", "non-carrier"], "article_id"=>421231, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Telomere_length_in_affected_BRCA1_2_mutation_carriers_and_corresponding_non_carrier_sisters_/421231", "title"=>"Telomere length in affected BRCA1/2 mutation carriers and corresponding non-carrier sisters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:10:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/751313"], "description"=>"<p>Mean age of cancer development in mothers and daughters in the three groups, BRCA1, BRCA2 and BRCAX, of hereditary breast cancer. Statistical significance of the difference between mothers and daughters was estimated by t-tests.</p><p>s.d. Standard deviation. Bilateral <i>t</i>-test was performed to assess the significance of the differences between mothers and daughters. Values for the <i>t</i>-statistic and the <i>p</i>-value for the <i>t</i>-test are indicated.</p>", "links"=>[], "tags"=>["onset", "cancer", "mothers", "daughters", "hereditary"], "article_id"=>421680, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Difference_in_the_age_of_onset_of_breast_cancer_between_mothers_and_daughters_in_hereditary_breast_cancer_/421680", "title"=>"Difference in the age of onset of breast cancer between mothers and daughters in hereditary breast cancer.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 16:16:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/751349"], "description"=>"<p>Data from the mother-daughter pairs from familial breast cancer families showing the age of breast cancer diagnosis, or age at interview of unaffected daughters, and the age-adjusted telomere length.</p><p>BR: Breast cancer, BR Bi: Bilateral Breast cancer, OV: Ovarian cancer.</p>", "links"=>[], "tags"=>["telomere", "mother-daughter", "pairs", "unaffected"], "article_id"=>421716, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.t004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_adjusted_telomere_length_in_mother_daughter_pairs_with_unaffected_BRCA1_2_carrier_daughters_/421716", "title"=>"Age-adjusted telomere length in mother-daughter pairs with unaffected BRCA1/2 carrier daughters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/750680"], "description"=>"<p>Telomere length distribution in peripheral blood leukocytes as a function of age for the control women population (n = 267, grey circles) and for breast cancer cases (black circles). Controls show the expected telomere length erosion with increasing age. Regression line for controls is drawn (y = −0.0146x+1.585, R<sup>2</sup> = 0.144). Comparison between control telomere length distribution and telomeres from 48 BRCA1 (A), 44 BRCA2 (B), 105 BRCAX (C), and 71 sporadic breast cancer cases (D) is represented.</p>", "links"=>[], "tags"=>["familial", "sporadic", "cancer"], "article_id"=>421045, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Telomere_length_distribution_in_control_familial_breast_cancer_and_sporadic_breast_cancer_cases_/421045", "title"=>"Telomere length distribution in control, familial breast cancer, and sporadic breast cancer cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:09:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/750779"], "description"=>"<p>Age-adjusted telomere length (calculated as the difference between the observed and the predicted values; see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002182#s4\" target=\"_blank\">Materials and Methods</a> section) distribution in peripheral blood leukocytes of control women (n = 267); familial breast cancer groups BRCA1 (n = 48), BRCA2 (n = 45), and BRCAX (n = 105); and sporadic breast cancer (n = 71). Bilateral <i>t</i>-tests were performed to compare telomeres of breast cancer groups with the controls and the respective <i>p</i>-values are represented. Significantly shorter telomeres were found in all hereditary breast cancer groups whereas no significant differences appeared between controls and sporadic breast cancer cases.</p>", "links"=>[], "tags"=>["telomere", "adjusted", "women", "hereditary", "sporadic"], "article_id"=>421142, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_telomere_length_adjusted_for_age_in_control_women_and_hereditary_and_sporadic_breast_cancer_/421142", "title"=>"Comparison of telomere length, adjusted for age, in control women and hereditary and sporadic breast cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:10:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/751002"], "description"=>"<p>Open circles (females) and squares (males) represent normal individuals and black circles represent affected females. Age of breast cancer diagnosis is shown for affected women. Mother-daughter pairs where the telomere length was studied are highlighted and age-adjusted telomere length for each pair is represented in the graphic below the pedigrees.</p>", "links"=>[], "tags"=>["cancer", "pedigrees", "anticipation", "onset"], "article_id"=>421371, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Familial_breast_cancer_pedigrees_showing_anticipation_in_the_age_of_onset_of_breast_cancer_/421371", "title"=>"Familial breast cancer pedigrees showing anticipation in the age of onset of breast cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 16:11:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/751231"], "description"=>"<p>BRCAX families were stratified according to the number of generations with affected breast cancer cases and distributed into the quartiles of telomere length.</p>", "links"=>[], "tags"=>["brcax", "quartiles", "telomere"], "article_id"=>421597, "categories"=>["Cancer", "Genetics"], "users"=>["Beatriz Martinez-Delgado", "Kira Yanowsky", "Lucía Inglada-Pérez", "Samuel Domingo", "Miguel Urioste", "Ana Osorio", "Javier Benitez"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002182.t002", "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_BRCAX_families_in_the_quartiles_of_telomere_length_/421597", "title"=>"Distribution of BRCAX families in the quartiles of telomere length.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 16:15:55"}

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