Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma

Abstract Mutations in genes of the breast cancer susceptibility gene (BRCA) pathway, namely, BRCA1, BRCA2, and PALB2, can provide useful information for the efficacy of platinum-based or poly ADP-ribose polymerase inhibitors chemotherapeutic regimens. Pancreatic ductal adenocarcinoma (PDAC) is an im...

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Autores principales:	Shoko Takeuchi, Manami Doi, Naoki Ikari, Masakazu Yamamoto, Toru Furukawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d40c23707883482abf91327dc831d1da
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spelling	oai:doaj.org-article:d40c23707883482abf91327dc831d1da2021-12-02T15:08:44ZMutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma10.1038/s41598-018-26526-x2045-2322https://doaj.org/article/d40c23707883482abf91327dc831d1da2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-26526-xhttps://doaj.org/toc/2045-2322Abstract Mutations in genes of the breast cancer susceptibility gene (BRCA) pathway, namely, BRCA1, BRCA2, and PALB2, can provide useful information for the efficacy of platinum-based or poly ADP-ribose polymerase inhibitors chemotherapeutic regimens. Pancreatic ductal adenocarcinoma (PDAC) is an important target for such precision chemotherapies because of its dismal prognosis. We analyzed mutations in the entire coding regions of the BRCA pathway genes, expression of breast cancer 2 (BRCA2), and mutations in hotspots of 50 cancer-associated genes in 42 surgically resected PDACs, and evaluated their associations with clinicopathological features. We identified 13 rare germline mutations in the BRCA pathway genes; 68 somatic mutations in KRAS, TP53, SMAD4, CDKN2A, GNAS, SMARCB1, and RB1; and 2 germline variations in MLH1. Among them, BRCA2 S2148fs was known to be pathogenic. BRCA2 R18H and BRCA2 G2044V were enriched in tumor tissues. BRCA2 K799R and BRCA2 R2964T were novel germline variations. Patients harboring potentially deleterious mutations in the BRCA pathway genes showed significantly better prognosis than those with benign mutations or no mutation. These results indicate that rare germline variations in BRCA pathway genes could be found more frequently than previously anticipated and, more importantly, potentially deleterious mutations of them could be a favorable prognostic factor in patients with resectable PDACs.Shoko TakeuchiManami DoiNaoki IkariMasakazu YamamotoToru FurukawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shoko Takeuchi Manami Doi Naoki Ikari Masakazu Yamamoto Toru Furukawa Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
description	Abstract Mutations in genes of the breast cancer susceptibility gene (BRCA) pathway, namely, BRCA1, BRCA2, and PALB2, can provide useful information for the efficacy of platinum-based or poly ADP-ribose polymerase inhibitors chemotherapeutic regimens. Pancreatic ductal adenocarcinoma (PDAC) is an important target for such precision chemotherapies because of its dismal prognosis. We analyzed mutations in the entire coding regions of the BRCA pathway genes, expression of breast cancer 2 (BRCA2), and mutations in hotspots of 50 cancer-associated genes in 42 surgically resected PDACs, and evaluated their associations with clinicopathological features. We identified 13 rare germline mutations in the BRCA pathway genes; 68 somatic mutations in KRAS, TP53, SMAD4, CDKN2A, GNAS, SMARCB1, and RB1; and 2 germline variations in MLH1. Among them, BRCA2 S2148fs was known to be pathogenic. BRCA2 R18H and BRCA2 G2044V were enriched in tumor tissues. BRCA2 K799R and BRCA2 R2964T were novel germline variations. Patients harboring potentially deleterious mutations in the BRCA pathway genes showed significantly better prognosis than those with benign mutations or no mutation. These results indicate that rare germline variations in BRCA pathway genes could be found more frequently than previously anticipated and, more importantly, potentially deleterious mutations of them could be a favorable prognostic factor in patients with resectable PDACs.
format	article
author	Shoko Takeuchi Manami Doi Naoki Ikari Masakazu Yamamoto Toru Furukawa
author_facet	Shoko Takeuchi Manami Doi Naoki Ikari Masakazu Yamamoto Toru Furukawa
author_sort	Shoko Takeuchi
title	Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
title_short	Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
title_full	Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
title_fullStr	Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
title_full_unstemmed	Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
title_sort	mutations in brca1, brca2, and palb2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d40c23707883482abf91327dc831d1da
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Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma

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