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dc.contributor.authorHemminger, Jessica A
dc.contributor.authorPearlman, Rachel
dc.contributor.authorHaraldsdottir, Sigurdis
dc.contributor.authorKnight, Deborah
dc.contributor.authorJonasson, Jon Gunnlaugur
dc.contributor.authorPritchard, Colin C
dc.contributor.authorHampel, Heather
dc.contributor.authorFrankel, Wendy L
dc.date.accessioned2018-10-25T15:35:48Z
dc.date.available2018-10-25T15:35:48Z
dc.date.issued2018-08-01
dc.date.submitted2018-10
dc.identifier.citationHistology of colorectal adenocarcinoma with Check for double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome. 2018, 78: 125-130 Human Pathology
dc.identifier.issn1532-8392
dc.identifier.pmid29723603
dc.identifier.doi10.1016/j.humpath.2018.04.017
dc.identifier.urihttp://hdl.handle.net/2336/620711
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractLynch syndrome (LS) is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development. Universal tumor screening for LS is routinely performed on colon cancer, and screening has identified patients with unexplained MMR deficiency that lack MLH1 methylation and a germline mutation. Tumor sequencing has since identified double somatic (DS) mutations in the MMR gene corresponding with the absent protein in 69% of these patients. We assessed whether histomorphology could distinguish patients with DS mutations from those with LS. Colorectal cancer patients with DS mutations were identified from population-based cohorts from Iceland (2000-2009); Columbus, Ohio (1999-2005); and the state of Ohio (2013-2016). Next-generation sequencing was performed on tumors with unexplained MMR deficiency. Patients with LS from Ohio cohorts were the comparison group. The histologic features associated with MMR deficiency (tumor-infiltrating lymphocytes, Crohn-like reaction, histologic subtype, necrosis) were evaluated. We identified 43 tumors with DS mutations and 48 from patients with LS. There was no significant difference in histologic features between tumors in LS patients and tumors with DS mutations. Because histology of tumors with DS mutations is indistinguishable from those caused by LS, tumor sequencing for evaluation of DS mutations should be considered to help clarify sporadic versus hereditary causes of unexplained MMR deficiency.en_US
dc.description.sponsorshipPelotonia, an annual cycling event in Columbus, Ohio National Cancer Institute, Bethesda, MDen_US
dc.language.isoenen_US
dc.publisherW B SAUNDERS CO-ELSEVIER INCen_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0046817718301461en_US
dc.subjectBiallelic mutationsen_US
dc.subjectDouble somatic mutationsen_US
dc.subjectLynch syndromeen_US
dc.subjectLynch-like syndromeen_US
dc.subjectMMR deficiencyen_US
dc.subjectRistilkrabbameinen_US
dc.subjectVefjafræðien_US
dc.subject.meshColorectal Neoplasmsen_US
dc.subject.meshAdenocarcinomaen_US
dc.titleHistology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome.en_US
dc.typeArticleen_US
dc.contributor.department[ 1 ] Ohio State Univ, Wexner Med Ctr, Dept Pathol, Columbus, OH 43210 USA Show more [ 2 ] Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA Show more [ 3 ] Stanford Univ, Med Ctr, Dept Med Oncol, Stanford, CA 94305 USA Show more [ 4 ] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland Show more [ 5 ] Univ Washington, Dept Lab Med, Seattle, WA 98195 USAen_US
dc.identifier.journalHuman Pathologyen_US
dc.rights.accessNational Consortium - Landsaðganguren_US
dc.departmentcodePTT12
dc.source.journaltitleHuman pathology


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