{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:27:39Z","timestamp":1776180459960,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["ProMark project 202059"],"award-info":[{"award-number":["ProMark project 202059"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000806","name":"European Environment Agency","doi-asserted-by":"publisher","award":["RO14\u20100017"],"award-info":[{"award-number":["RO14\u20100017"]}],"id":[{"id":"10.13039\/501100000806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000806","name":"European Environment Agency","doi-asserted-by":"publisher","award":["EEAJRP\u2010RO\u2010NO\u201020131\u201010191"],"award-info":[{"award-number":["EEAJRP\u2010RO\u2010NO\u201020131\u201010191"]}],"id":[{"id":"10.13039\/501100000806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,12]]},"abstract":"Abstract<\/jats:title>Two familial forms of colorectal cancer (CRC<\/jats:styled-content>), Lynch syndrome (LS<\/jats:styled-content>) and familial adenomatous polyposis (FAP<\/jats:styled-content>), are caused by rare mutations in DNA<\/jats:styled-content> mismatch repair genes (MLH<\/jats:styled-content>1<\/jats:italic>, MSH<\/jats:styled-content>2<\/jats:italic>, MSH<\/jats:styled-content>6<\/jats:italic>, PMS<\/jats:styled-content>2<\/jats:italic>) and the genes APC<\/jats:styled-content><\/jats:italic> and MUTYH<\/jats:styled-content><\/jats:italic>, respectively. No information is available on the presence of high\u2010risk CRC<\/jats:styled-content> mutations in the Romanian population. We performed whole\u2010genome sequencing of 61 Romanian CRC<\/jats:styled-content> cases with a family history of cancer and\/or early onset of disease, focusing the analysis on candidate variants in the LS<\/jats:styled-content> and FAP<\/jats:styled-content> genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC<\/jats:styled-content> cases and 4567 controls. Immunohistochemical (IHC<\/jats:styled-content>) staining for MLH<\/jats:styled-content>1<\/jats:italic>, MSH<\/jats:styled-content>2<\/jats:italic>, MSH<\/jats:styled-content>6<\/jats:italic>, and PMS<\/jats:styled-content>2<\/jats:italic> was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH<\/jats:styled-content>1<\/jats:italic>, one in MSH<\/jats:styled-content>6<\/jats:italic>, one in PMS<\/jats:styled-content>2<\/jats:italic>, and three in APC<\/jats:styled-content><\/jats:italic>. Combining information on the predicted impact of the variants on the proteins, IHC<\/jats:styled-content> results and previous reports, we found three novel pathogenic variants (MLH<\/jats:styled-content>1<\/jats:italic>:p.Lys84ThrfsTer4, MLH<\/jats:styled-content>1<\/jats:italic>:p.Ala586CysfsTer7, PMS<\/jats:styled-content>2<\/jats:italic>:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS<\/jats:styled-content> variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH<\/jats:styled-content>1<\/jats:italic>:c.1559\u20101G>C).<\/jats:p>","DOI":"10.1111\/jcmm.13881","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T07:58:40Z","timestamp":1539676720000},"page":"6068-6076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of Lynch syndrome risk variants in the Romanian population"],"prefix":"10.1111","volume":"22","author":[{"given":"Paul D.","family":"Iordache","sequence":"first","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"},{"name":"School of Science and Engineering Reykjavik University Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Mates","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarni","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannes P.","family":"Eggertsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Sulem","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Benonisdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma Eva","family":"Csiki","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Rascu","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Radavoi","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu","family":"Ursu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine \u201cCarol Davila\u201d University of Medicine and Pharmacy Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalin","family":"Staicu","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Calota","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Voinoiu","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Jinga","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central University Emergency Military Hospital Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Rosoga","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Razvan","family":"Danau","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorin Cristian","family":"Sima","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Badescu","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoleta","family":"Suciu","sequence":"additional","affiliation":[{"name":"National Institute of Public Health Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viorica","family":"Radoi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine \u201cCarol Davila\u201d University of Medicine and Pharmacy Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioan Nicolae","family":"Mates","sequence":"additional","affiliation":[{"name":"St. Mary\u201d General Surgery Clinic University of Medicine and Pharmacy Carol Davila Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Dobra","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camelia","family":"Nicolae","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrun","family":"Kristjansdottir","sequence":"additional","affiliation":[{"name":"Department of Pathology Landspitali University Hospital Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon G.","family":"Jonasson","sequence":"additional","affiliation":[{"name":"Department of Pathology Landspitali University Hospital Reykjavik Iceland"},{"name":"Faculty of Medicine School of Health Sciences, University of Iceland Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Manolescu","sequence":"additional","affiliation":[{"name":"School of Science and Engineering Reykjavik University Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudny","family":"Arnadottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brynjar","family":"Jensson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aslaug","family":"Jonasdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asgeir","family":"Sigurdsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"le Roux","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrefna","family":"Johannsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorunn","family":"Rafnar","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarni V.","family":"Halldorsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"},{"name":"School of Science and Engineering Reykjavik University Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viorel","family":"Jinga","sequence":"additional","affiliation":[{"name":"Urology Department \u2018Prof. Dr. Th. Burghele\u2019 Clinical Hospital, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/AMGEN Reykjavik Iceland"},{"name":"Faculty of Medicine School of Health Sciences, University of Iceland Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25516"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805213382101"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27996"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-004-7993-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-011-9465-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14755"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.184"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-016-9884-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.3119"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200011000-00012"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_7_13_1","unstructured":"Picard Tools \u2013 By Broad Institute n.d.http:\/\/broadinstitute.github.io\/picard\/. Accessed July 6 2018."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2017.115"},{"key":"e_1_2_7_17_1","first-page":"201","article-title":"Analysis of protein\u2010coding genetic variation in 60,706 humans","volume":"106","author":"Lek M","year":"2017","journal-title":"Nature"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.190"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.060"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0869-4"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13881","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13881","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T02:21:19Z","timestamp":1694744479000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":20,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1111\/jcmm.13881"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13881","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,16]]},"assertion":[{"value":"2018-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}