Unknown

Dataset Information

0

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

ABSTRACT: 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.

SUBMITTER: Haraldsdottir S 

PROVIDER: S-EPMC5418568 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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 def  ...[more]

Similar Datasets

Unknown Characterization of two Ashkenazi Jewish founder mutations in MSH6 gene causing Lynch syndrome.
| S-EPMC4541773 | biostudies-literature
Unknown MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer.
| S-EPMC2890527 | biostudies-literature
Unknown MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer.
| S-EPMC6051923 | biostudies-literature
Unknown Early age of onset and broad cancer spectrum persist in MSH6- and PMS2-associated Lynch syndrome.
| S-EPMC9942243 | biostudies-literature
Unknown The changing landscape of Lynch syndrome due to PMS2 mutations.
| S-EPMC5995637 | biostudies-literature
Unknown The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.
| S-EPMC2759321 | biostudies-literature
Unknown Recurrent and founder mutations in the PMS2 gene.
| S-EPMC3445698 | biostudies-literature
Unknown SNP association study in PMS2-associated Lynch syndrome.
| S-EPMC6182583 | biostudies-literature
Unknown Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair.
| S-EPMC2908215 | biostudies-literature
Unknown Risks of Lynch syndrome cancers for MSH6 mutation carriers.
| S-EPMC2815724 | biostudies-literature