Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/96874 |
Resumo: | Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings. |
id |
RCAP_2383fbba3c1583a461765df2aacf2bfe |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/96874 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancerDetectionEpigeneticsHomologous recombination DNA repairMale breast cancerCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistrySDG 3 - Good Health and Well-beingBackground: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNAndré, SaudadeNunes, Sandra P.Silva, FernandaHenrique, RuiFélix, AnaJerónimo, Carmen2020-04-27T22:32:04Z2020-042020-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/96874eng1661-6596PURE: 17934062https://doi.org/10.3390/ijms21082715info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:44:18Zoai:run.unl.pt:10362/96874Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:38:39.261232Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
title |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
spellingShingle |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer André, Saudade Detection Epigenetics Homologous recombination DNA repair Male breast cancer Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
title_short |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
title_full |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
title_fullStr |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
title_full_unstemmed |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
title_sort |
Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer |
author |
André, Saudade |
author_facet |
André, Saudade Nunes, Sandra P. Silva, Fernanda Henrique, Rui Félix, Ana Jerónimo, Carmen |
author_role |
author |
author2 |
Nunes, Sandra P. Silva, Fernanda Henrique, Rui Félix, Ana Jerónimo, Carmen |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
dc.contributor.author.fl_str_mv |
André, Saudade Nunes, Sandra P. Silva, Fernanda Henrique, Rui Félix, Ana Jerónimo, Carmen |
dc.subject.por.fl_str_mv |
Detection Epigenetics Homologous recombination DNA repair Male breast cancer Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
topic |
Detection Epigenetics Homologous recombination DNA repair Male breast cancer Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
description |
Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-04-27T22:32:04Z 2020-04 2020-04-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/96874 |
url |
http://hdl.handle.net/10362/96874 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1661-6596 PURE: 17934062 https://doi.org/10.3390/ijms21082715 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799138003045580800 |