Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study
In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-bas...
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| Veröffentlicht in: | PloS one 2019-01, Vol.14 (1), p.e0210372 |
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| creator | Olivier, Magali Bouaoun, Liacine Villar, Stephanie Robitaille, Alexis Cahais, Vincent Heguy, Adriana Byrnes, Graham Le Calvez-Kelm, Florence Torres-Mejía, Gabriela Alvarado-Cabrero, Isabel Imani-Razavi, Fazlollah Shahram Inés Sánchez, Gloria Jaramillo, Roberto Porras, Carolina Rodriguez, Ana Cecilia Garmendia, Maria Luisa Soto, José Luis Romieu, Isabelle Porter, Peggy Guenthoer, Jamie Rinaldi, Sabina |
| description | In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.
Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.
The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.
These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors. |
| doi_str_mv | 10.1371/journal.pone.0210372 |
| format | Article |
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Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.
The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.
These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0210372</identifier><identifier>PMID: 30653559</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; AKT1 protein ; Analysis ; Biology and Life Sciences ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast Neoplasms - epidemiology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Carcinogens ; Case-Control Studies ; Deoxyribonucleic acid ; DNA ; DNA repair ; DNA sequencing ; Epidermal growth factor receptors ; ErbB-2 protein ; Exome Sequencing ; Female ; Gene sequencing ; Genes ; Genes, p53 ; Genetic aspects ; Health aspects ; Health risk assessment ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Incidence ; Latin America - epidemiology ; Medicine and Health Sciences ; Menopause ; Middle Aged ; Mutation ; p53 Protein ; Paraffin ; Paraffins ; Pathology ; Pilot Projects ; Population studies ; Populations ; Premenopause - genetics ; Premenopause - metabolism ; Proteins ; Research and Analysis Methods ; Risk analysis ; Risk factors ; Signatures ; Studies ; Tissues ; Transduction ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors ; Women's health ; Young Adult</subject><ispartof>PloS one, 2019-01, Vol.14 (1), p.e0210372</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Olivier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Olivier et al 2019 Olivier et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c743t-af87b86d44c37f310de6b22f47ec8a66b146959d0a0b8f274559547cb01ef29d3</citedby><cites>FETCH-LOGICAL-c743t-af87b86d44c37f310de6b22f47ec8a66b146959d0a0b8f274559547cb01ef29d3</cites><orcidid>0000-0003-4000-9280 ; 0000-0002-8202-342X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336331/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336331/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30653559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bandapalli, Obul Reddy</contributor><creatorcontrib>Olivier, Magali</creatorcontrib><creatorcontrib>Bouaoun, Liacine</creatorcontrib><creatorcontrib>Villar, Stephanie</creatorcontrib><creatorcontrib>Robitaille, Alexis</creatorcontrib><creatorcontrib>Cahais, Vincent</creatorcontrib><creatorcontrib>Heguy, Adriana</creatorcontrib><creatorcontrib>Byrnes, Graham</creatorcontrib><creatorcontrib>Le Calvez-Kelm, Florence</creatorcontrib><creatorcontrib>Torres-Mejía, Gabriela</creatorcontrib><creatorcontrib>Alvarado-Cabrero, Isabel</creatorcontrib><creatorcontrib>Imani-Razavi, Fazlollah Shahram</creatorcontrib><creatorcontrib>Inés Sánchez, Gloria</creatorcontrib><creatorcontrib>Jaramillo, Roberto</creatorcontrib><creatorcontrib>Porras, Carolina</creatorcontrib><creatorcontrib>Rodriguez, Ana Cecilia</creatorcontrib><creatorcontrib>Garmendia, Maria Luisa</creatorcontrib><creatorcontrib>Soto, José Luis</creatorcontrib><creatorcontrib>Romieu, Isabelle</creatorcontrib><creatorcontrib>Porter, Peggy</creatorcontrib><creatorcontrib>Guenthoer, Jamie</creatorcontrib><creatorcontrib>Rinaldi, Sabina</creatorcontrib><creatorcontrib>PRECAMA team</creatorcontrib><creatorcontrib>on behalf of the PRECAMA team</creatorcontrib><title>Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.
Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.
The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.
These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.</description><subject>Adult</subject><subject>AKT1 protein</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - epidemiology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Carcinogens</subject><subject>Case-Control Studies</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA repair</subject><subject>DNA sequencing</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB-2 protein</subject><subject>Exome Sequencing</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genes, p53</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Incidence</subject><subject>Latin America - epidemiology</subject><subject>Medicine and Health Sciences</subject><subject>Menopause</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>Pathology</subject><subject>Pilot Projects</subject><subject>Population studies</subject><subject>Populations</subject><subject>Premenopause - genetics</subject><subject>Premenopause - metabolism</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Signatures</subject><subject>Studies</subject><subject>Tissues</subject><subject>Transduction</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><subject>Women's health</subject><subject>Young 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features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study</title><author>Olivier, Magali ; Bouaoun, Liacine ; Villar, Stephanie ; Robitaille, Alexis ; Cahais, Vincent ; Heguy, Adriana ; Byrnes, Graham ; Le Calvez-Kelm, Florence ; Torres-Mejía, Gabriela ; Alvarado-Cabrero, Isabel ; Imani-Razavi, Fazlollah Shahram ; Inés Sánchez, Gloria ; Jaramillo, Roberto ; Porras, Carolina ; Rodriguez, Ana Cecilia ; Garmendia, Maria Luisa ; Soto, José Luis ; Romieu, Isabelle ; Porter, Peggy ; Guenthoer, Jamie ; Rinaldi, Sabina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c743t-af87b86d44c37f310de6b22f47ec8a66b146959d0a0b8f274559547cb01ef29d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>AKT1 protein</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers, Tumor - 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Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olivier, Magali</au><au>Bouaoun, Liacine</au><au>Villar, Stephanie</au><au>Robitaille, Alexis</au><au>Cahais, Vincent</au><au>Heguy, Adriana</au><au>Byrnes, Graham</au><au>Le Calvez-Kelm, Florence</au><au>Torres-Mejía, Gabriela</au><au>Alvarado-Cabrero, Isabel</au><au>Imani-Razavi, Fazlollah Shahram</au><au>Inés Sánchez, Gloria</au><au>Jaramillo, Roberto</au><au>Porras, Carolina</au><au>Rodriguez, Ana Cecilia</au><au>Garmendia, Maria Luisa</au><au>Soto, José Luis</au><au>Romieu, Isabelle</au><au>Porter, Peggy</au><au>Guenthoer, Jamie</au><au>Rinaldi, Sabina</au><au>Bandapalli, Obul Reddy</au><aucorp>PRECAMA team</aucorp><aucorp>on behalf of the PRECAMA team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-01-17</date><risdate>2019</risdate><volume>14</volume><issue>1</issue><spage>e0210372</spage><pages>e0210372-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.
Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.
The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.
These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30653559</pmid><doi>10.1371/journal.pone.0210372</doi><tpages>e0210372</tpages><orcidid>https://orcid.org/0000-0003-4000-9280</orcidid><orcidid>https://orcid.org/0000-0002-8202-342X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-01, Vol.14 (1), p.e0210372 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2168179322 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult AKT1 protein Analysis Biology and Life Sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast cancer Breast Neoplasms - epidemiology Breast Neoplasms - genetics Breast Neoplasms - metabolism Carcinogens Case-Control Studies Deoxyribonucleic acid DNA DNA repair DNA sequencing Epidermal growth factor receptors ErbB-2 protein Exome Sequencing Female Gene sequencing Genes Genes, p53 Genetic aspects Health aspects Health risk assessment High-Throughput Nucleotide Sequencing Humans Immunohistochemistry Incidence Latin America - epidemiology Medicine and Health Sciences Menopause Middle Aged Mutation p53 Protein Paraffin Paraffins Pathology Pilot Projects Population studies Populations Premenopause - genetics Premenopause - metabolism Proteins Research and Analysis Methods Risk analysis Risk factors Signatures Studies Tissues Transduction Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors Women's health Young Adult |
| title | Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study |
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