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Identification of Lynch syndrome risk variants in the Romanian population

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dc.contributor Háskólinn í Reykjavík
dc.contributor Reykjavik University
dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Iordache, Paul
dc.contributor.author Mates, Dana
dc.contributor.author Gunnarsson, Bjarni
dc.contributor.author Eggertsson, Hannes
dc.contributor.author sulem, patrick
dc.contributor.author Benonisdottir, Stefania
dc.contributor.author Csiki, Irma Eva
dc.contributor.author Rascu, Stefan
dc.contributor.author Radavoi, Daniel
dc.contributor.author Ursu, Radu
dc.contributor.author Staicu, Catalin
dc.contributor.author Calota, Violeta
dc.contributor.author Voinoiu, Angelica
dc.contributor.author Jinga, Mariana
dc.contributor.author Rosoga, Gabriel
dc.contributor.author Danau, Razvan
dc.contributor.author Sima, Sorin Cristian
dc.contributor.author Badescu, Daniel
dc.contributor.author Suciu, Nicoleta
dc.contributor.author Radoi, Viorica
dc.contributor.author Mates, Ioan Nicolae
dc.contributor.author Dobra, Mihai
dc.contributor.author Nicolae, Camelia
dc.contributor.author Kristjansdottir, Sigrun
dc.contributor.author Jónasson, Jón G.
dc.contributor.author Manolescu, Andrei
dc.contributor.author Arnadottir, Gudny
dc.contributor.author Jensson, Brynjar Örn
dc.contributor.author Jonasdottir, Aslaug
dc.contributor.author Sigurdsson, Asgeir
dc.contributor.author le Roux, Louise
dc.contributor.author Johannsdottir, Hrefna
dc.contributor.author Rafnar, Thorunn
dc.contributor.author Halldórsson, Bjarni
dc.contributor.author Jinga, Viorel
dc.contributor.author Stefansson, Kari
dc.date.accessioned 2019-10-09T14:50:47Z
dc.date.available 2019-10-09T14:50:47Z
dc.date.issued 2018-10-16
dc.identifier.citation Iordache, PD, Mates, D, Gunnarsson, B, et al. Identification of Lynch syndrome risk variants in the Romanian population. J Cell Mol Med. 2018; 22: 6068– 6076. https://doi.org/10.1111/jcmm.13881
dc.identifier.issn 1582-1838
dc.identifier.issn 1582-4934 (eISSN)
dc.identifier.uri https://hdl.handle.net/20.500.11815/1301
dc.description Publisher's version (útgefin grein)
dc.description.abstract Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high‐risk CRC mutations in the Romanian population. We performed whole‐genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559‐1G>C).
dc.description.sponsorship This study was funded in part by the European Union FP7 Program (ProMark project 202059) and by the EEA grant (ROMCAN project RO14‐0017; EEAJRP‐RO‐NO‐20131‐10191). We thank the study participants, the staff at deCODE Genetics Iceland and Landspitali University Hospital.
dc.format.extent 6068-6076
dc.language.iso en
dc.publisher Wiley
dc.relation info:eu-repo/grantAgreement/EC/FP7/202059
dc.relation.ispartofseries Journal of Cellular and Molecular Medicine;22(12)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Colorectal cancer
dc.subject Lynch syndrome
dc.subject Romania
dc.subject Endaþarmskrabbamein
dc.subject Lynch heilkenni
dc.subject Rúmenía
dc.title Identification of Lynch syndrome risk variants in the Romanian population
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
dc.description.version Peer Reviewed
dc.identifier.journal Journal of Cellular and Molecular Medicine
dc.identifier.doi 10.1111/jcmm.13881
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Tækni- og verkfræðideild (HR)
dc.contributor.school School of Science and Engineering (RU)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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