Opin vísindi

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2


Titill: Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2
Höfundur: Haraldsdottir, Sigurdis   orcid.org/0000-0002-5050-3699
Rafnar, Þórunn
Frankel, Wendy L.
Einarsdóttir, Sylvía
Sigurðsson, Ásgeir
Hampel, Heather
Snaebjornsson, Petur   orcid.org/0000-0002-1086-8108
Másson, Gísli   orcid.org/0000-0003-0493-8242
Weng, Daniel
Arngrimsson, Reynir   orcid.org/0000-0003-1142-2914
... 17 fleiri höfundar Sýna alla höfunda
Útgáfa: 2017-05-03
Tungumál: Enska
Umfang: 14755
Háskóli/Stofnun: Háskóli Íslands
University of Iceland
Svið: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Deild: Læknadeild (HÍ)
Faculty of Medicine (UI)
Birtist í: Nature Communications;8
ISSN: 2041-1723
DOI: 10.1038/ncomms14755
Efnisorð: Cancer epidemiology; Cancer genetics; Cancer genomics; Krabbamein; Krabbameinsrannsóknir; Arfgengi; Erfðagreining
URI: https://hdl.handle.net/20.500.11815/374

Skoða fulla færslu

Tilvitnun:

Haraldsdottir, S. et al. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2. Nat. Commun. 8, 14755 doi: 10.1038/ncomms14755 (2017).

Útdráttur:

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000–2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

Leyfi:

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Skrár

Þetta verk birtist í eftirfarandi safni/söfnum:


Fletta

Um vefinn

Reikningurinn minn