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

Autor:	Cereda M; Division of Cancer Studies, King's College London, London SE1 1UL, UK., Gambardella G; Division of Cancer Studies, King's College London, London SE1 1UL, UK., Benedetti L; Division of Cancer Studies, King's College London, London SE1 1UL, UK., Iannelli F; IFOM, FIRC Institute of Molecular Oncology, Milan 20139, Italy., Patel D; Department of Research Pathology, Cancer Institute, University College London, London WC1E 6JJ, UK., Basso G; Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Research Hospital, Rozzano (MI) 20089, Italy., Guerra RF; Department of Craniofacial Development &Stem Cell Biology, King's College London, London SE1 9RT, UK., Mourikis TP; Division of Cancer Studies, King's College London, London SE1 1UL, UK., Puccio I; Department of Research Pathology, Cancer Institute, University College London, London WC1E 6JJ, UK., Sinha S; Division of Cancer Studies, King's College London, London SE1 1UL, UK., Laghi L; Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Research Hospital, Rozzano (MI) 20089, Italy., Spencer J; Department of Immunobiology, King's College London, London, SE1 9RT, UK., Rodriguez-Justo M; Department of Research Pathology, Cancer Institute, University College London, London WC1E 6JJ, UK., Ciccarelli FD; Division of Cancer Studies, King's College London, London SE1 1UL, UK.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2016 Jul 05; Vol. 7, pp. 12072. Date of Electronic Publication: 2016 Jul 05.
DOI:	10.1038/ncomms12072
Abstrakt:	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.
Databáze:	MEDLINE
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