Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-21

AUTHORS

Ulrika A. Hänninen, Erkki-Ville Wirta, Riku Katainen, Tomas Tanskanen, Jiri Hamberg, Minna Taipale, Jan Böhm, Laura Renkonen-Sinisalo, Anna Lepistö, Linda M. Forsström, Esa Pitkänen, Kimmo Palin, Toni T. Seppälä, Netta Mäkinen, Jukka-Pekka Mecklin, Lauri A. Aaltonen

ABSTRACT

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy. More... »

PAGES

1-9

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41416-019-0427-4

DOI

http://dx.doi.org/10.1038/s41416-019-0427-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112881134

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30894686


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