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) |