University of Oulu

Karihtala, P., Porvari, K., & Kilpivaara, O. (2022). Mutational signatures associate with survival in gastrointestinal carcinomas. Cancer Genomics - Proteomics, 19(5), 556–569.

Mutational signatures associate with survival in gastrointestinal carcinomas

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Author: Karihtala, Peeter1; Porvari, Katja2; Kilpivaara, Outi3,4,5
Organizations: 1Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
2Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
4Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
5HUSLAB Laboratory of Genetics, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.5 MB)
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Language: English
Published: International Institute of Anticancer Research, 2022
Publish Date: 2023-03-20


Background/Aim: Mutational signatures reflect common patterns based on the counts of mutations and their sequence context. The prognostic value of these signatures, mirroring various carcinogenetic processes of cancers, are unexplored in gastrointestinal cancers. Our aim was to evaluate possible prognostic relevance of mutational signatures in gastrointestinal carcinomas after adjusting with the traditional prognostic factors.

Materials and Methods: We used publicly available data from The Cancer Genome Atlas and Pan-Cancer Analysis of Whole Genomes to evaluate the associations between survival endpoints and activity of mutational signatures in seven types of gastrointestinal cancers.

Results: Most strikingly, the high activity of age-related single-base substitution 5 (SBS5) and SBS40 signatures were in rectal adenocarcinomas associated with both improved overall survival (OS) [for SBS5 hazard ratio (HR) 0.130; 95% CI=0.03‐0.56, for SBS40 HR=0.072; 95% CI=0.012‐0.44, respectively] and similarly also to rectal cancer-specific survival. In patients with left-sided (but not right-sided) colon adenocarcinoma, the high activity of SBS2 signatures, formed due to APOBEC activity, predicted shortened OS. In pancreatic cancer, the high activity of SBS10b, caused by polymerase epsilon exonuclease proofreading defects, was associated both with longer OS (HR=0.44; 95% CI=0.205‐0.96) and pancreatic cancer-specific survival (HR=0.32; 95% CI=0.112‐0.91).

Conclusions: Several mutational signatures seem to have clinically meaningful, cancer-specific associations with prognosis among gastrointestinal cancers.

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Series: Cancer genomics & proteomics
ISSN: 1109-6535
ISSN-E: 1790-6245
ISSN-L: 1109-6535
Volume: 19
Issue: 5
Pages: 556 - 569
DOI: 10.21873/cgp.20340
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3111 Biomedicine
Copyright information: © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (