Author:
Nguyen Bastien,Sanchez-Vega Francisco,Fong Christopher J.,Chatila Walid K.,Boroujeni Amir Momeni,Pareja Fresia,Weigelt Britta,Sotiriou Christos,Larsimont Denis,Reis-Filho Jorge S.,Desmedt Christine,Schultz Nikolaus
Abstract
AbstractMucinous 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.
Funder
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, a National Cancer Institute Cancer Center Core Grant
Breast Cancer Research Foundation
Congressionally Directed Medical Research Programs
Thompson Family Foundation
Robertson Foundation
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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