Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel
Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-gene...
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| description | Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling. |
| doi_str_mv | 10.1371/journal.pone.0291015 |
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However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0291015</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Age ; Analysis ; Arab people ; Biology and Life Sciences ; BRCA1 protein ; BRCA2 protein ; Breast cancer ; Care and treatment ; Colorectal cancer ; Diagnosis ; DNA repair ; DNA sequencing ; Epidemiology ; Ethnicity ; Family medical history ; Genes ; Genetic analysis ; Genetic counseling ; Genetic screening ; Genetic testing ; Genetics ; Genomes ; Medical diagnosis ; Medicine and Health Sciences ; Metastasis ; MLH3 gene ; Next-generation sequencing ; Nucleotide sequencing ; Ovarian cancer ; Ovaries ; Pms1 gene ; Population studies ; Prostate ; Prostate cancer ; Risk assessment ; Sequence analysis ; Womens health</subject><ispartof>PloS one, 2023-09, Vol.18 (9), p.e0291015-e0291015</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Al-Kafaji 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>2023 Al-Kafaji et al 2023 Al-Kafaji et al</rights><rights>2023 Al-Kafaji 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c619t-776c4e156937fc57d5bcd43deeb4c8e844467e33e1d9699bf686bb9c97bb4d953</cites><orcidid>0000-0002-8397-3689</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/PMC10473515/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473515/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids></links><search><creatorcontrib>Al-Kafaji, Ghada</creatorcontrib><creatorcontrib>Jassim, Ghufran</creatorcontrib><creatorcontrib>AlHajeri, Amani</creatorcontrib><creatorcontrib>Alawadhi, Amna Mohamed Tayeb</creatorcontrib><creatorcontrib>Fida, Mariam</creatorcontrib><creatorcontrib>Sahin, Ibrahim</creatorcontrib><creatorcontrib>Alali, Faisal</creatorcontrib><creatorcontrib>Fadel, Elias</creatorcontrib><title>Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel</title><title>PloS one</title><description>Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. 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Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.</description><subject>Age</subject><subject>Analysis</subject><subject>Arab people</subject><subject>Biology and Life Sciences</subject><subject>BRCA1 protein</subject><subject>BRCA2 protein</subject><subject>Breast cancer</subject><subject>Care and treatment</subject><subject>Colorectal cancer</subject><subject>Diagnosis</subject><subject>DNA repair</subject><subject>DNA sequencing</subject><subject>Epidemiology</subject><subject>Ethnicity</subject><subject>Family medical history</subject><subject>Genes</subject><subject>Genetic analysis</subject><subject>Genetic counseling</subject><subject>Genetic screening</subject><subject>Genetic testing</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Medical diagnosis</subject><subject>Medicine 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Elias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel</atitle><jtitle>PloS one</jtitle><date>2023-09-01</date><risdate>2023</risdate><volume>18</volume><issue>9</issue><spage>e0291015</spage><epage>e0291015</epage><pages>e0291015-e0291015</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0291015</doi><tpages>e0291015</tpages><orcidid>https://orcid.org/0000-0002-8397-3689</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Age Analysis Arab people Biology and Life Sciences BRCA1 protein BRCA2 protein Breast cancer Care and treatment Colorectal cancer Diagnosis DNA repair DNA sequencing Epidemiology Ethnicity Family medical history Genes Genetic analysis Genetic counseling Genetic screening Genetic testing Genetics Genomes Medical diagnosis Medicine and Health Sciences Metastasis MLH3 gene Next-generation sequencing Nucleotide sequencing Ovarian cancer Ovaries Pms1 gene Population studies Prostate Prostate cancer Risk assessment Sequence analysis Womens health |
| title | Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel |
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