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

Matteo Cereda, Gennaro Gambardella, Lorena Benedetti, Fabio Iannelli, Dominic Patel, Gianluca Basso, Rosalinda F. Guerra, Thanos P. Mourikis, Ignazio Puccio, Shruti Sinha, Luigi Laghi, Jo Spencer, Manuel Rodriguez-Justo, Francesca D. Ciccarelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number12072
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Jul 5 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes'. Together they form a unique fingerprint.

Cite this