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Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes.


ABSTRACT: Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy and in the monitoring of resistance. SyCRC patients show a higher occurrence of inherited damaging mutations in immune-related genes compared to patients with solitary colorectal cancer and to healthy individuals from the 1,000 Genomes Project. Moreover, they have a different composition of immune cell populations in tumour and normal mucosa, and transcriptional differences in immune-related biological processes. This suggests an environmental field effect that promotes multiple tumours likely in the background of inflammation.

SUBMITTER: Cereda M 

PROVIDER: S-EPMC4935966 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes.

Cereda Matteo M   Gambardella Gennaro G   Benedetti Lorena L   Iannelli Fabio F   Patel Dominic D   Basso Gianluca G   Guerra Rosalinda F RF   Mourikis Thanos P TP   Puccio Ignazio I   Sinha Shruti S   Laghi Luigi L   Spencer Jo J   Rodriguez-Justo Manuel M   Ciccarelli Francesca D FD  

Nature communications 20160705


Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy  ...[more]

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