Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2
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 pathogenici...
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ftwestvirginiaun:oai:researchrepository.wvu.edu:faculty_publications-2618 2023-12-03T10:24:42+01:00 Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 Haraldsdottir, Sigurdis Rafnar, Thorunn Frankel, Wendy L Einarsdottir, Sylvia Sigurdsson, Asgeir Hampel, Heather Snaebjornsson, Petur Masson, Gisli Weng, Daniel Arngrimsson, Reynir Kehr, Birte Yilmaz, Ahmet Haraldsson, Stefan Sulem, Patrick Stefansson, Tryggvi Shields, Peter G Sigurdsson, Fridjorn Bekaii-Saab, Tanios Moller, Pall H Steinarsdottir, Margret Alexiusdottir, Kristin Hitchins, Megan Pritchard, Coiln C Chapelle, Albert de la Jonasson, Jon G Goldberg, Richard M Stefansson, Kari 2017-01-01T08:00:00Z application/pdf https://researchrepository.wvu.edu/faculty_publications/1699 https://researchrepository.wvu.edu/context/faculty_publications/article/2618/viewcontent/ncomms14755.pdf unknown The Research Repository @ WVU https://researchrepository.wvu.edu/faculty_publications/1699 https://researchrepository.wvu.edu/context/faculty_publications/article/2618/viewcontent/ncomms14755.pdf Faculty & Staff Scholarship text 2017 ftwestvirginiaun 2023-11-05T18:00:35Z 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 MSH6and 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 PMS2prevail in Iceland unlike most other populations. Text Iceland The Research Repository @ WVU (West Virginia University) Lynch ENVELOPE(-57.683,-57.683,-63.783,-63.783) |
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The Research Repository @ WVU (West Virginia University) |
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ftwestvirginiaun |
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description |
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 MSH6and 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 PMS2prevail in Iceland unlike most other populations. |
format |
Text |
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Haraldsdottir, Sigurdis Rafnar, Thorunn Frankel, Wendy L Einarsdottir, Sylvia Sigurdsson, Asgeir Hampel, Heather Snaebjornsson, Petur Masson, Gisli Weng, Daniel Arngrimsson, Reynir Kehr, Birte Yilmaz, Ahmet Haraldsson, Stefan Sulem, Patrick Stefansson, Tryggvi Shields, Peter G Sigurdsson, Fridjorn Bekaii-Saab, Tanios Moller, Pall H Steinarsdottir, Margret Alexiusdottir, Kristin Hitchins, Megan Pritchard, Coiln C Chapelle, Albert de la Jonasson, Jon G Goldberg, Richard M Stefansson, Kari |
spellingShingle |
Haraldsdottir, Sigurdis Rafnar, Thorunn Frankel, Wendy L Einarsdottir, Sylvia Sigurdsson, Asgeir Hampel, Heather Snaebjornsson, Petur Masson, Gisli Weng, Daniel Arngrimsson, Reynir Kehr, Birte Yilmaz, Ahmet Haraldsson, Stefan Sulem, Patrick Stefansson, Tryggvi Shields, Peter G Sigurdsson, Fridjorn Bekaii-Saab, Tanios Moller, Pall H Steinarsdottir, Margret Alexiusdottir, Kristin Hitchins, Megan Pritchard, Coiln C Chapelle, Albert de la Jonasson, Jon G Goldberg, Richard M Stefansson, Kari Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
author_facet |
Haraldsdottir, Sigurdis Rafnar, Thorunn Frankel, Wendy L Einarsdottir, Sylvia Sigurdsson, Asgeir Hampel, Heather Snaebjornsson, Petur Masson, Gisli Weng, Daniel Arngrimsson, Reynir Kehr, Birte Yilmaz, Ahmet Haraldsson, Stefan Sulem, Patrick Stefansson, Tryggvi Shields, Peter G Sigurdsson, Fridjorn Bekaii-Saab, Tanios Moller, Pall H Steinarsdottir, Margret Alexiusdottir, Kristin Hitchins, Megan Pritchard, Coiln C Chapelle, Albert de la Jonasson, Jon G Goldberg, Richard M Stefansson, Kari |
author_sort |
Haraldsdottir, Sigurdis |
title |
Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
title_short |
Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
title_full |
Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
title_fullStr |
Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
title_full_unstemmed |
Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2 |
title_sort |
comprehensive population-wide analysis of lynch syndrome in iceland reveals founder mutations in msh6 and pms2 |
publisher |
The Research Repository @ WVU |
publishDate |
2017 |
url |
https://researchrepository.wvu.edu/faculty_publications/1699 https://researchrepository.wvu.edu/context/faculty_publications/article/2618/viewcontent/ncomms14755.pdf |
long_lat |
ENVELOPE(-57.683,-57.683,-63.783,-63.783) |
geographic |
Lynch |
geographic_facet |
Lynch |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Faculty & Staff Scholarship |
op_relation |
https://researchrepository.wvu.edu/faculty_publications/1699 https://researchrepository.wvu.edu/context/faculty_publications/article/2618/viewcontent/ncomms14755.pdf |
_version_ |
1784273213490987008 |