Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer

Abstract Both non-small-cell lung cancer cases in never-smokers and nonmedullary thyroid cancer cases have been increasing in developed countries. Some studies have shown an excess of co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. We aimed to clarify the underlying gene...

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Autores principales:	Shiro Fujita, Katsuhiro Masago
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ae9bd9405f5415286a09199ca3fcf2c
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spelling	oai:doaj.org-article:4ae9bd9405f5415286a09199ca3fcf2c2021-12-02T12:09:50ZAlteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer10.1038/s41598-021-83177-12045-2322https://doaj.org/article/4ae9bd9405f5415286a09199ca3fcf2c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83177-1https://doaj.org/toc/2045-2322Abstract Both non-small-cell lung cancer cases in never-smokers and nonmedullary thyroid cancer cases have been increasing in developed countries. Some studies have shown an excess of co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. We aimed to clarify the underlying genetic factors that contribute to the occurrence of these two malignancies. We performed germline exome sequencing in a cohort of 9 patients with the two malignancies. In terms of candidate genes, we performed target resequencing, immunohistochemistry, and microsatellite instability testing on another cohort. Two rare missense heterozygous variants in MSH6 were identified and verified by Sanger sequencing. One available tumour specimen showed heterogeneous MSH6 status in immunohistochemistry. Further exploration with different cohorts (a total of 8 patients with the two malignancies) demonstrated that 2 out of 8 patients had a germline missense or promotor variant of MLH1 and four out of 10 tumour specimens revealed heterogeneous immunohistochemistry staining in any of the four mismatch repair proteins: MLH1, PMS2, MSH2 and MSH6. Although our cohort showed a different disease profile than Lynch syndrome, this study suggests causal roles of impaired DNA mismatch repair capacity in non-small-cell lung cancer and nonmedullary thyroid cancer.Shiro FujitaKatsuhiro MasagoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shiro Fujita Katsuhiro Masago Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
description	Abstract Both non-small-cell lung cancer cases in never-smokers and nonmedullary thyroid cancer cases have been increasing in developed countries. Some studies have shown an excess of co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. We aimed to clarify the underlying genetic factors that contribute to the occurrence of these two malignancies. We performed germline exome sequencing in a cohort of 9 patients with the two malignancies. In terms of candidate genes, we performed target resequencing, immunohistochemistry, and microsatellite instability testing on another cohort. Two rare missense heterozygous variants in MSH6 were identified and verified by Sanger sequencing. One available tumour specimen showed heterogeneous MSH6 status in immunohistochemistry. Further exploration with different cohorts (a total of 8 patients with the two malignancies) demonstrated that 2 out of 8 patients had a germline missense or promotor variant of MLH1 and four out of 10 tumour specimens revealed heterogeneous immunohistochemistry staining in any of the four mismatch repair proteins: MLH1, PMS2, MSH2 and MSH6. Although our cohort showed a different disease profile than Lynch syndrome, this study suggests causal roles of impaired DNA mismatch repair capacity in non-small-cell lung cancer and nonmedullary thyroid cancer.
format	article
author	Shiro Fujita Katsuhiro Masago
author_facet	Shiro Fujita Katsuhiro Masago
author_sort	Shiro Fujita
title	Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
title_short	Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
title_full	Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
title_fullStr	Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
title_full_unstemmed	Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
title_sort	alteration of dna mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4ae9bd9405f5415286a09199ca3fcf2c
work_keys_str_mv	AT shirofujita alterationofdnamismatchrepaircapacityunderlyingthecooccurrenceofnonsmallcelllungcancerandnonmedullarythyroidcancer AT katsuhiromasago alterationofdnamismatchrepaircapacityunderlyingthecooccurrenceofnonsmallcelllungcancerandnonmedullarythyroidcancer
_version_	1718394626121924608

Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer

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