{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:16:50Z","timestamp":1758845810376,"version":"3.44.0"},"reference-count":19,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2019,10,5]]},"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>An obligate germline Lynch syndrome carrier had four colonic adenomas removed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and methods<\/jats:title>\n                  <jats:p>The adenomas were evaluated for grade of dysplasia, MLH1, PMS2, MSH2 and MSH6 protein expression, microsatellite instability (MSI), <jats:italic>BRAF<\/jats:italic>, methylation status and a next-generation sequencing (NGS) panel of 52 cancer genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There were four tubular or tubulovillous adenomas from the hepatic flexure, rectosigmoid and rectum; one with low-grade and high-grade dysplasia, one with high-grade dysplasia only and two with low-grade dysplasia. All four adenomas showed retention of MLH1, MHS2 and MSH6 but complete loss of PMS2 in both low-grade and high-grade dysplasia areas.<\/jats:p>\n                  <jats:p>Two of the four adenomas were MSI-high, <jats:italic>BRAF V600E<\/jats:italic> wild type and were not <jats:italic>MLH1<\/jats:italic> methylated. NGS identified an <jats:italic>MLH1<\/jats:italic> germline variant: NM_000249.3: c.1558+1 G&gt;A, p.(?) in all tissue (adenomas and normal), which likely explains the pathophysiology of Lynch syndrome in this patient. Other variants were also detected in <jats:italic>MLH1<\/jats:italic> and <jats:italic>MSH6<\/jats:italic> in all four adenomas tested; these being reported previously in somatic colorectal cancers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We highlight an <jats:italic>MLH1<\/jats:italic> variant in the colonic adenomas in an obligate Lynch syndrome carrier that resulted in PMS2 protein loss in the absence of mutations of the <jats:italic>PMS2<\/jats:italic> gene.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2019-206234","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T17:15:33Z","timestamp":1571937333000},"page":"291-295","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Unique <i>MLH1<\/i> mutations in colonic adenomas in an obligate germline Lynch syndrome carrier"],"prefix":"10.1136","volume":"73","author":[{"given":"Stefano","family":"Serra","sequence":"first","affiliation":[{"name":"Laboratory Medicine Program, Divisions of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose-Mario","family":"Capo-Chichi","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Genetics, University Health Network, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-0924","authenticated-orcid":false,"given":"Aoife J","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Program, Divisions of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Genetics, University Health Network, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-515X","authenticated-orcid":false,"given":"Runjan","family":"Chetty","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Program, Divisions of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, 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