{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:38:59Z","timestamp":1793893139741,"version":"4.8.0"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Deparmetnt Operating Expenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We report the first pedigree of Lynch syndrome bearing a germ-line MSH2 missense mutation c.1808A&amp;gt;T (Asp603Val). Until now, this missense mutation, in exon 12 of MSH2, was identified as a variant of unknown significance in the International Society for Gastrointestinal Hereditary Tumours database. In vitro induction mutagenesis experiments indicated that the MSH2 mutant protein (Asp603Val) is easily degraded in embryonic stem cells, albeit there is no clinical information concerning this mutant. Our pedigree includes four patients with Lynch syndrome-associated malignancies and clinically matches the Amsterdam II criteria. The proband, a female, first had an endometrial cancer at the age of 49 and then mantle cell lymphoma, colonic and gastric adenocarcinomas and neuroendocrine carcinoma, successively. Her mother also had Lynch syndrome-associated malignancies, including colonic, uterine and gastric cancers, and her elder son had rectal cancer. In the germline of the proband and her son, an MSH2 missense mutation c.1808A&amp;gt;T was discovered. Immunohistochemical analyses indicated that the expression of the MSH2 protein was decreased in the tumors, such as gastric cancer and neuroendocrine carcinoma, due to the missense mutation c.1808A&amp;gt;T. This study showed that the MSH2 missense mutation c.1808A&amp;gt;T (Asp603Val) is a likely pathogenic mutation and is responsible for typical Lynch syndrome-associated malignancies, including neuroendocrine carcinoma.<\/jats:p>","DOI":"10.1093\/jjco\/hyab173","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T18:21:20Z","timestamp":1634754080000},"page":"81-85","source":"Crossref","is-referenced-by-count":6,"title":["A novel Lynch syndrome pedigree bearing germ-line <i>MSH2<\/i> missense mutation c.1808A&amp;gt;T (Asp603Val)"],"prefix":"10.1093","volume":"52","author":[{"given":"Risako","family":"Sekine","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Shimazu","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8454-1995","authenticated-orcid":false,"given":"Tatsuro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusato","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Neurology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Neurology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nanjyo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Akita University Hospital, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3581-3506","authenticated-orcid":false,"given":"Hiroyuki","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"2022010310245775500_ref1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1155\/2004\/305058","article-title":"Mutations associated with HNPCC predisposition\u2013update of ICG-HNPCC\/INSiGHT mutation database","volume":"20","author":"Peltomaki","year":"2004","journal-title":"Dis 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syndrome","volume":"8","author":"Serracant","year":"2017","journal-title":"J Gastrointest Oncol"},{"key":"2022010310245775500_ref8","first-page":"95","article-title":"A molecularly confirmed neuroendocrine tumor resulting from Lynch syndrome","volume":"4","author":"Sorscher","year":"2013","journal-title":"J Gastrointest Oncol"},{"key":"2022010310245775500_ref9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/gutjnl-2015-309675","article-title":"Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database","volume":"66","author":"M\u00f8ller","year":"2017","journal-title":"Gut"},{"key":"2022010310245775500_ref10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ejca.2018.02.021","article-title":"Comprehensive analysis of cancers of unknown primary for the biomarkers of response to immune checkpoint blockade 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