TY - JOUR
T1 - Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes
AU - Cereda, Matteo
AU - Gambardella, Gennaro
AU - Benedetti, Lorena Gabriela
AU - Iannelli, Fabio
AU - Patel, Dominic
AU - Basso, Gianluca
AU - Guerra, Rosalinda
AU - Mourikis, Thanos P.
AU - Puccio, Ignazio
AU - Sinha, Shruti
AU - Laghi, Luigi
AU - Spencer, Jo
AU - Rodriguez-Justo, Manuel
AU - Ciccarelli, Francesca Donatella
PY - 2016/7/5
Y1 - 2016/7/5
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms12072
DO - 10.1038/ncomms12072
M3 - Article
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 12072
ER -