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

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...

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Autores principales: Hänninen, Ulrika A., Wirta, Erkki-Ville, Katainen, Riku, Tanskanen, Tomas, Hamberg, Jiri, Taipale, Minna, Böhm, Jan, Renkonen-Sinisalo, Laura, Lepistö, Anna, Forsström, Linda M., Pitkänen, Esa, Palin, Kimmo, Seppälä, Toni T., Mäkinen, Netta, Mecklin, Jukka-Pekka, Aaltonen, Lauri A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734647/
https://www.ncbi.nlm.nih.gov/pubmed/30894686
http://dx.doi.org/10.1038/s41416-019-0427-4
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author Hänninen, Ulrika A.
Wirta, Erkki-Ville
Katainen, Riku
Tanskanen, Tomas
Hamberg, Jiri
Taipale, Minna
Böhm, Jan
Renkonen-Sinisalo, Laura
Lepistö, Anna
Forsström, Linda M.
Pitkänen, Esa
Palin, Kimmo
Seppälä, Toni T.
Mäkinen, Netta
Mecklin, Jukka-Pekka
Aaltonen, Lauri A.
author_facet Hänninen, Ulrika A.
Wirta, Erkki-Ville
Katainen, Riku
Tanskanen, Tomas
Hamberg, Jiri
Taipale, Minna
Böhm, Jan
Renkonen-Sinisalo, Laura
Lepistö, Anna
Forsström, Linda M.
Pitkänen, Esa
Palin, Kimmo
Seppälä, Toni T.
Mäkinen, Netta
Mecklin, Jukka-Pekka
Aaltonen, Lauri A.
author_sort Hänninen, Ulrika A.
collection PubMed
description 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.
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spelling pubmed-67346472020-03-21 Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers Hänninen, Ulrika A. Wirta, Erkki-Ville Katainen, Riku Tanskanen, Tomas Hamberg, Jiri Taipale, Minna Böhm, Jan Renkonen-Sinisalo, Laura Lepistö, Anna Forsström, Linda M. Pitkänen, Esa Palin, Kimmo Seppälä, Toni T. Mäkinen, Netta Mecklin, Jukka-Pekka Aaltonen, Lauri A. Br J Cancer Article 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. Nature Publishing Group UK 2019-03-21 2019-04-30 /pmc/articles/PMC6734647/ /pubmed/30894686 http://dx.doi.org/10.1038/s41416-019-0427-4 Text en © Cancer Research UK 2019 https://creativecommons.org/licenses/by/4.0/This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Hänninen, Ulrika A.
Wirta, Erkki-Ville
Katainen, Riku
Tanskanen, Tomas
Hamberg, Jiri
Taipale, Minna
Böhm, Jan
Renkonen-Sinisalo, Laura
Lepistö, Anna
Forsström, Linda M.
Pitkänen, Esa
Palin, Kimmo
Seppälä, Toni T.
Mäkinen, Netta
Mecklin, Jukka-Pekka
Aaltonen, Lauri A.
Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title_full Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title_fullStr Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title_full_unstemmed Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title_short Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
title_sort exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734647/
https://www.ncbi.nlm.nih.gov/pubmed/30894686
http://dx.doi.org/10.1038/s41416-019-0427-4
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