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

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 h...

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Published inNature communications Vol. 7; no. 1; pp. 12072 - 12
Main Authors 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.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 05.07.2016
Nature Publishing Group
Nature Portfolio
Subjects
13/51
38/91
631/208/68
631/208/737
631/67/2329
692/699/67/1504/1885
Cloning
Colorectal cancer
Colorectal carcinoma
Gastroenterology
Genomes
Heterogeneity
Humanities and Social Sciences
multidisciplinary
Mutation
Science
Science (multidisciplinary)
Tumors
United Kingdom > UK
Italy
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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. Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing strategy to show that the synchronous tumours are genetically independent and the patients harbour rare germline damaging mutations in genes associated with the immune system.
AbstractList Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing strategy to show that the synchronous tumours are genetically independent and the patients harbour rare germline damaging mutations in genes associated with the immune system.
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.
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. Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing strategy to show that the synchronous tumours are genetically independent and the patients harbour rare germline damaging mutations in genes associated with the immune system.
ArticleNumber 12072
Author Spencer, Jo
Rodriguez-Justo, Manuel
Gambardella, Gennaro
Benedetti, Lorena
Puccio, Ignazio
Patel, Dominic
Laghi, Luigi
Mourikis, Thanos P.
Basso, Gianluca
Cereda, Matteo
Guerra, Rosalinda F.
Iannelli, Fabio
Sinha, Shruti
Ciccarelli, Francesca D.
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  email: francesca.ciccarelli@kcl.ac.uk
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/27377421$$D View this record in MEDLINE/PubMed
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Snippet Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental...
Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing...
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SubjectTerms 13/51
38/91
631/208/68
631/208/737
631/67/2329
692/699/67/1504/1885
Cloning
Colorectal cancer
Colorectal carcinoma
Gastroenterology
Genomes
Heterogeneity
Humanities and Social Sciences
multidisciplinary
Mutation
Science
Science (multidisciplinary)
Tumors
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Title Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes
URI https://link.springer.com/article/10.1038/ncomms12072
https://www.ncbi.nlm.nih.gov/pubmed/27377421
https://www.proquest.com/docview/1801619047
https://pubmed.ncbi.nlm.nih.gov/PMC4935966
https://doaj.org/article/53dd8c3165584a758cf01d490afce229
Volume 7
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