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

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

Original languageEnglish
Article number12072
Number of pages12
JournalNature Communications
Issue number1
Accepted/In press26 May 2016
Published5 Jul 2016


King's Authors


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 1000 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.

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