Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer
Germline variants inactivating the mismatch repair (MMR) genesMLH1,MSH2,MSH6andPMS2cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients wi...
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| description | Germline variants inactivating the mismatch repair (MMR) genesMLH1,MSH2,MSH6andPMS2cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes. |
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C. C.</contributor><creatorcontrib>Singh, Ashish Kumar ; Talseth-Palmer, Bente ; McPhillips, Mary ; Lavik, Liss Anne Solberg ; Xavier, Alexandre ; Drablos, Finn ; Sjursen, Wenche ; de Miranda, Noel F. C. C.</creatorcontrib><description>Germline variants inactivating the mismatch repair (MMR) genesMLH1,MSH2,MSH6andPMS2cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0235613</identifier><identifier>PMID: 32634176</identifier><language>eng</language><publisher>SAN FRANCISCO: Public Library Science</publisher><subject>Annotations ; Bioinformatics ; Biology and life sciences ; Cancer ; Colon ; Colon cancer ; Colorectal cancer ; Computer programs ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA mismatch repair ; DNA sequencing ; Endometrial cancer ; Endometrium ; Exons ; Gene sequencing ; Genes ; Genetic aspects ; Genetic disorders ; Genetics ; Genomes ; Health aspects ; Health risks ; Health sciences ; Hospitals ; Medical research ; Medicine ; Medicine and Health Sciences ; Mismatch repair ; MLH1 protein ; MSH2 protein ; MSH6 protein ; Multidisciplinary Sciences ; Mutation ; Next-generation sequencing ; Pathogenicity ; Pathogens ; Patients ; Pharmacy ; R&D ; Repair ; Research & development ; Research and Analysis Methods ; Risk ; Science & Technology ; Science & Technology - Other Topics ; Software ; Software development tools ; Uterine cancer ; Womens health</subject><ispartof>PloS one, 2020-07, Vol.15 (7), p.e0235613-e0235613, Article 0235613</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Singh 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. 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C. C.</contributor><creatorcontrib>Singh, Ashish Kumar</creatorcontrib><creatorcontrib>Talseth-Palmer, Bente</creatorcontrib><creatorcontrib>McPhillips, Mary</creatorcontrib><creatorcontrib>Lavik, Liss Anne Solberg</creatorcontrib><creatorcontrib>Xavier, Alexandre</creatorcontrib><creatorcontrib>Drablos, Finn</creatorcontrib><creatorcontrib>Sjursen, Wenche</creatorcontrib><title>Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer</title><title>PloS one</title><addtitle>PLOS ONE</addtitle><description>Germline variants inactivating the mismatch repair (MMR) genesMLH1,MSH2,MSH6andPMS2cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. 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sciences</subject><subject>Hospitals</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mismatch repair</subject><subject>MLH1 protein</subject><subject>MSH2 protein</subject><subject>MSH6 protein</subject><subject>Multidisciplinary Sciences</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Patients</subject><subject>Pharmacy</subject><subject>R&D</subject><subject>Repair</subject><subject>Research & development</subject><subject>Research and Analysis Methods</subject><subject>Risk</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Software</subject><subject>Software development tools</subject><subject>Uterine cancer</subject><subject>Womens 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sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer</title><author>Singh, Ashish Kumar ; Talseth-Palmer, Bente ; McPhillips, Mary ; Lavik, Liss Anne Solberg ; Xavier, Alexandre ; Drablos, Finn ; Sjursen, Wenche</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-b88bb4a28f1f1f46024151b1a8ab88a1ee6073120975bef29e5d61b97ef2e00b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Annotations</topic><topic>Bioinformatics</topic><topic>Biology and life sciences</topic><topic>Cancer</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Computer programs</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA mismatch repair</topic><topic>DNA sequencing</topic><topic>Endometrial 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C. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer</atitle><jtitle>PloS one</jtitle><stitle>PLOS ONE</stitle><date>2020-07-07</date><risdate>2020</risdate><volume>15</volume><issue>7</issue><spage>e0235613</spage><epage>e0235613</epage><pages>e0235613-e0235613</pages><artnum>0235613</artnum><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Germline variants inactivating the mismatch repair (MMR) genesMLH1,MSH2,MSH6andPMS2cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. 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| subjects | Annotations Bioinformatics Biology and life sciences Cancer Colon Colon cancer Colorectal cancer Computer programs Deoxyribonucleic acid DNA DNA methylation DNA mismatch repair DNA sequencing Endometrial cancer Endometrium Exons Gene sequencing Genes Genetic aspects Genetic disorders Genetics Genomes Health aspects Health risks Health sciences Hospitals Medical research Medicine Medicine and Health Sciences Mismatch repair MLH1 protein MSH2 protein MSH6 protein Multidisciplinary Sciences Mutation Next-generation sequencing Pathogenicity Pathogens Patients Pharmacy R&D Repair Research & development Research and Analysis Methods Risk Science & Technology Science & Technology - Other Topics Software Software development tools Uterine cancer Womens health |
| title | Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T20%3A59%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targeted%20sequencing%20of%20genes%20associated%20with%20the%20mismatch%20repair%20pathway%20in%20patients%20with%20endometrial%20cancer&rft.jtitle=PloS%20one&rft.au=Singh,%20Ashish%20Kumar&rft.date=2020-07-07&rft.volume=15&rft.issue=7&rft.spage=e0235613&rft.epage=e0235613&rft.pages=e0235613-e0235613&rft.artnum=0235613&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0235613&rft_dat=%3Cgale_pubme%3EA628802086%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2421072499&rft_id=info:pmid/32634176&rft_galeid=A628802086&rft_doaj_id=oai_doaj_org_article_9a8406190f7b400fa9ed6324be034dce&rfr_iscdi=true |