Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

Abstract Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27...

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Autores principales:	Paula Sánchez-Fernández, Cristina Riobello, María Costales, Blanca Vivanco, Virginia N. Cabal, Rocío García-Marín, Laura Suárez-Fernández, Fernando López, Rubén Cabanillas, Mario A. Hermsen, José Luis Llorente
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c08e99b4a0ff4671bdd31432d99b0386
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spelling	oai:doaj.org-article:c08e99b4a0ff4671bdd31432d99b03862021-12-02T14:16:34ZNext-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma10.1038/s41598-020-80242-z2045-2322https://doaj.org/article/c08e99b4a0ff4671bdd31432d99b03862021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80242-zhttps://doaj.org/toc/2045-2322Abstract Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.Paula Sánchez-FernándezCristina RiobelloMaría CostalesBlanca VivancoVirginia N. CabalRocío García-MarínLaura Suárez-FernándezFernando LópezRubén CabanillasMario A. HermsenJosé Luis LlorenteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paula Sánchez-Fernández Cristina Riobello María Costales Blanca Vivanco Virginia N. Cabal Rocío García-Marín Laura Suárez-Fernández Fernando López Rubén Cabanillas Mario A. Hermsen José Luis Llorente Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
description	Abstract Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.
format	article
author	Paula Sánchez-Fernández Cristina Riobello María Costales Blanca Vivanco Virginia N. Cabal Rocío García-Marín Laura Suárez-Fernández Fernando López Rubén Cabanillas Mario A. Hermsen José Luis Llorente
author_facet	Paula Sánchez-Fernández Cristina Riobello María Costales Blanca Vivanco Virginia N. Cabal Rocío García-Marín Laura Suárez-Fernández Fernando López Rubén Cabanillas Mario A. Hermsen José Luis Llorente
author_sort	Paula Sánchez-Fernández
title	Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
title_short	Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
title_full	Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
title_fullStr	Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
title_full_unstemmed	Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
title_sort	next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c08e99b4a0ff4671bdd31432d99b0386
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Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

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