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 journalArticle

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

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Germ-Line Mutation
mutations
genes
Tumors
Colorectal Neoplasms
tumors
Genes
cancer
Neoplasms
Biological Phenomena
genome
Chemical analysis
therapy
Mucous Membrane
Clone Cells
Cells
occurrences
Genome
Inflammation
Mutation

ASJC Scopus subject areas

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

Cite this

Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes. / Cereda, Matteo; Gambardella, Gennaro; Benedetti, Lorena; Iannelli, Fabio; Patel, Dominic; Basso, Gianluca; Guerra, Rosalinda F.; Mourikis, Thanos P.; Puccio, Ignazio; Sinha, Shruti; Laghi, Luigi; Spencer, Jo; Rodriguez-Justo, Manuel; Ciccarelli, Francesca D.

In: Nature Communications, Vol. 7, 12072, 05.07.2016.

Research output: Contribution to journalArticle

Cereda, M, Gambardella, G, Benedetti, L, Iannelli, F, Patel, D, Basso, G, Guerra, RF, Mourikis, TP, Puccio, I, Sinha, S, Laghi, L, Spencer, J, Rodriguez-Justo, M & Ciccarelli, FD 2016, 'Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes', Nature Communications, vol. 7, 12072. https://doi.org/10.1038/ncomms12072
Cereda, Matteo ; Gambardella, Gennaro ; Benedetti, Lorena ; Iannelli, Fabio ; Patel, Dominic ; Basso, Gianluca ; Guerra, Rosalinda F. ; Mourikis, Thanos P. ; Puccio, Ignazio ; Sinha, Shruti ; Laghi, Luigi ; Spencer, Jo ; Rodriguez-Justo, Manuel ; Ciccarelli, Francesca D. / Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes. In: Nature Communications. 2016 ; Vol. 7.
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