The genomic landscape of carcinomas with mucinous differentiation

Abstract Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types...

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Autores principales:	Bastien Nguyen, Francisco Sanchez-Vega, Christopher J. Fong, Walid K. Chatila, Amir Momeni Boroujeni, Fresia Pareja, Britta Weigelt, Christos Sotiriou, Denis Larsimont, Jorge S. Reis-Filho, Christine Desmedt, Nikolaus Schultz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c0bc9dd2f7f64c679e8a4095f00c5414
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spelling	oai:doaj.org-article:c0bc9dd2f7f64c679e8a4095f00c54142021-12-02T14:49:43ZThe genomic landscape of carcinomas with mucinous differentiation10.1038/s41598-021-89099-22045-2322https://doaj.org/article/c0bc9dd2f7f64c679e8a4095f00c54142021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89099-2https://doaj.org/toc/2045-2322Abstract Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types by comparing mucinous and non-mucinous samples, integrating text mining of pathology reports, gene expression, methylation, mutational and copy-number profiling. We found that, in addition to genes involved in mucin processing and secretion, MUC2 up-regulation is a multi-cancer biomarker of mucinous histology and is regulated by DNA methylation in colorectal, breast and stomach cancer. The majority of carcinomas with mucinous differentiation had fewer DNA copy-number alterations than non-mucinous tumors. The tumor mutational burden was lower in breast and lung with mucinous differentiation compared to their non-mucinous counterparts. We found several differences in the frequency of oncogenic gene and pathway alterations between mucinous and non-mucinous carcinomas, including a lower frequency of p53 pathway alterations in colorectal and lung cancer, and a lower frequency of PI-3-Kinase/Akt pathway alterations in breast and stomach cancer with mucinous differentiation. This study shows that carcinomas with mucinous differentiation originating from different organs share transcriptomic and genomic similarities. These results might pave the way for a more biologically relevant taxonomy for these rare cancers.Bastien NguyenFrancisco Sanchez-VegaChristopher J. FongWalid K. ChatilaAmir Momeni BoroujeniFresia ParejaBritta WeigeltChristos SotiriouDenis LarsimontJorge S. Reis-FilhoChristine DesmedtNikolaus SchultzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bastien Nguyen Francisco Sanchez-Vega Christopher J. Fong Walid K. Chatila Amir Momeni Boroujeni Fresia Pareja Britta Weigelt Christos Sotiriou Denis Larsimont Jorge S. Reis-Filho Christine Desmedt Nikolaus Schultz The genomic landscape of carcinomas with mucinous differentiation
description	Abstract Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types by comparing mucinous and non-mucinous samples, integrating text mining of pathology reports, gene expression, methylation, mutational and copy-number profiling. We found that, in addition to genes involved in mucin processing and secretion, MUC2 up-regulation is a multi-cancer biomarker of mucinous histology and is regulated by DNA methylation in colorectal, breast and stomach cancer. The majority of carcinomas with mucinous differentiation had fewer DNA copy-number alterations than non-mucinous tumors. The tumor mutational burden was lower in breast and lung with mucinous differentiation compared to their non-mucinous counterparts. We found several differences in the frequency of oncogenic gene and pathway alterations between mucinous and non-mucinous carcinomas, including a lower frequency of p53 pathway alterations in colorectal and lung cancer, and a lower frequency of PI-3-Kinase/Akt pathway alterations in breast and stomach cancer with mucinous differentiation. This study shows that carcinomas with mucinous differentiation originating from different organs share transcriptomic and genomic similarities. These results might pave the way for a more biologically relevant taxonomy for these rare cancers.
format	article
author	Bastien Nguyen Francisco Sanchez-Vega Christopher J. Fong Walid K. Chatila Amir Momeni Boroujeni Fresia Pareja Britta Weigelt Christos Sotiriou Denis Larsimont Jorge S. Reis-Filho Christine Desmedt Nikolaus Schultz
author_facet	Bastien Nguyen Francisco Sanchez-Vega Christopher J. Fong Walid K. Chatila Amir Momeni Boroujeni Fresia Pareja Britta Weigelt Christos Sotiriou Denis Larsimont Jorge S. Reis-Filho Christine Desmedt Nikolaus Schultz
author_sort	Bastien Nguyen
title	The genomic landscape of carcinomas with mucinous differentiation
title_short	The genomic landscape of carcinomas with mucinous differentiation
title_full	The genomic landscape of carcinomas with mucinous differentiation
title_fullStr	The genomic landscape of carcinomas with mucinous differentiation
title_full_unstemmed	The genomic landscape of carcinomas with mucinous differentiation
title_sort	genomic landscape of carcinomas with mucinous differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c0bc9dd2f7f64c679e8a4095f00c5414
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The genomic landscape of carcinomas with mucinous differentiation

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