Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome
Lynch syndrome (LS) is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development. Universal tumor screening for LS is routinely performed on c...
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ftpubmed:oai:pubmedcentral.nih.gov:6296362 2023-05-15T16:51:14+02:00 Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome Hemminger, Jessica A. Pearlman, Rachel Haraldsdottir, Sigurdis Knight, Deborah Jonasson, Jon Gunnlaugur Pritchard, Colin C. Hampel, Heather Frankel, Wendy L. 2018-05-01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296362/ http://www.ncbi.nlm.nih.gov/pubmed/29723603 https://doi.org/10.1016/j.humpath.2018.04.017 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296362/ http://www.ncbi.nlm.nih.gov/pubmed/29723603 http://dx.doi.org/10.1016/j.humpath.2018.04.017 Article Text 2018 ftpubmed https://doi.org/10.1016/j.humpath.2018.04.017 2019-08-04T00:19:28Z Lynch syndrome (LS) is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development. Universal tumor screening for LS is routinely performed on colon cancer, and screening has identified patients with unexplained MMR deficiency that lack MLH1 methylation and a germline mutation. Tumor sequencing has since identified double somatic (DS) mutations in the MMR gene corresponding with the absent protein in 69% of these patients. We assessed whether histomorphology could distinguish patients with DS mutations from those with LS. Colorectal cancer patients with DS mutations were identified from population-based cohorts from Iceland (2000–2009); Columbus, Ohio (1999–2005); and the state of Ohio (2013–2016). Next-generation sequencing was performed on tumors with unexplained MMR deficiency. Patients with LS from Ohio cohorts were the comparison group. The histologic features associated with MMR deficiency (tumor-infiltrating lymphocytes, Crohn-like reaction, histologic subtype, necrosis) were evaluated. We identified 43 tumors with DS mutations and 48 from patients with LS. There was no significant difference in histologic features between tumors in LS patients and tumors with DS mutations. Because histology of tumors with DS mutations is indistinguishable from those caused by LS, tumor sequencing for evaluation of DS mutations should be considered to help clarify sporadic versus hereditary causes of unexplained MMR deficiency. Text Iceland PubMed Central (PMC) Lynch ENVELOPE(-57.683,-57.683,-63.783,-63.783) Human Pathology 78 125 130 |
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Article Hemminger, Jessica A. Pearlman, Rachel Haraldsdottir, Sigurdis Knight, Deborah Jonasson, Jon Gunnlaugur Pritchard, Colin C. Hampel, Heather Frankel, Wendy L. Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
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Lynch syndrome (LS) is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development. Universal tumor screening for LS is routinely performed on colon cancer, and screening has identified patients with unexplained MMR deficiency that lack MLH1 methylation and a germline mutation. Tumor sequencing has since identified double somatic (DS) mutations in the MMR gene corresponding with the absent protein in 69% of these patients. We assessed whether histomorphology could distinguish patients with DS mutations from those with LS. Colorectal cancer patients with DS mutations were identified from population-based cohorts from Iceland (2000–2009); Columbus, Ohio (1999–2005); and the state of Ohio (2013–2016). Next-generation sequencing was performed on tumors with unexplained MMR deficiency. Patients with LS from Ohio cohorts were the comparison group. The histologic features associated with MMR deficiency (tumor-infiltrating lymphocytes, Crohn-like reaction, histologic subtype, necrosis) were evaluated. We identified 43 tumors with DS mutations and 48 from patients with LS. There was no significant difference in histologic features between tumors in LS patients and tumors with DS mutations. Because histology of tumors with DS mutations is indistinguishable from those caused by LS, tumor sequencing for evaluation of DS mutations should be considered to help clarify sporadic versus hereditary causes of unexplained MMR deficiency. |
format |
Text |
author |
Hemminger, Jessica A. Pearlman, Rachel Haraldsdottir, Sigurdis Knight, Deborah Jonasson, Jon Gunnlaugur Pritchard, Colin C. Hampel, Heather Frankel, Wendy L. |
author_facet |
Hemminger, Jessica A. Pearlman, Rachel Haraldsdottir, Sigurdis Knight, Deborah Jonasson, Jon Gunnlaugur Pritchard, Colin C. Hampel, Heather Frankel, Wendy L. |
author_sort |
Hemminger, Jessica A. |
title |
Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
title_short |
Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
title_full |
Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
title_fullStr |
Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
title_full_unstemmed |
Histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by Lynch syndrome |
title_sort |
histology of colorectal adenocarcinoma with double somatic mismatch-repair mutations is indistinguishable from those caused by lynch syndrome |
publishDate |
2018 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296362/ http://www.ncbi.nlm.nih.gov/pubmed/29723603 https://doi.org/10.1016/j.humpath.2018.04.017 |
long_lat |
ENVELOPE(-57.683,-57.683,-63.783,-63.783) |
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Lynch |
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Lynch |
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Iceland |
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Iceland |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296362/ http://www.ncbi.nlm.nih.gov/pubmed/29723603 http://dx.doi.org/10.1016/j.humpath.2018.04.017 |
op_doi |
https://doi.org/10.1016/j.humpath.2018.04.017 |
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Human Pathology |
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78 |
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125 |
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130 |
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1766041341607804928 |