Somatic hits in mismatch repair genes in colorectal cancer among non-seminoma testicular cancer survivors

Berbel L.M. Ykema, Emilie C.H. Breekveldt, Beatriz Carvalho, Tom van Wezel, Gerrit A. Meijer, Martijn Kerst, Michael Schaapveld, Flora E. van Leeuwen, Pétur Snæbjörnsson, Monique E. van Leerdam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Non-seminoma testicular cancer survivors (TCS) have an increased risk of developing colorectal cancer (CRC) when they have been treated with platinum-based chemotherapy. Previously we demonstrated that among Hodgkin lymphoma survivors (HLS) there is enrichment of rare mismatch repair (MMR) deficient (MMRd) CRCs with somatic hits in MMR genes. We speculate that this phenomenon could also occur among other cancer survivors. We therefore aim to determine the MMR status and its underlying mechanism in CRC among TCS (TCS-CRC). Methods: Thirty TCS-CRC, identified through the Dutch pathology registry, were analysed for MMR proteins by immunohistochemistry. Next-generation sequencing was performed in MMRd CRCs without MLH1 promoter hypermethylation (n = 4). Data were compared with a male cohort with primary CRC (P-CRC, n = 629). Results: MMRd was found in 17% of TCS-CRCs vs. 9% in P-CRC (p = 0.13). MMRd was more often caused by somatic double or single hit in MMR genes by mutation or loss of heterozygosity in TCS-CRCs (3/30 (10%) vs. 11/629 (2%) in P-CRCs (p < 0.01)). Conclusions: MMRd CRCs with somatic double or single hit are more frequent in this small cohort of TCS compared with P-CRC. Exposure to anticancer treatments appears to be associated with the development of these rare MMRd CRC among cancer survivors.

Original languageEnglish
Pages (from-to)1991-1996
Number of pages6
JournalBritish Journal of Cancer
Volume127
Issue number11
DOIs
Publication statusPublished - 10 Sep 2022

Bibliographical note

Funding Information:
This study received a grant from the Dutch Digestive Foundation (Maag-, lever-, darmstichting, MLDS) and Sacha Swarttouw-Hijmans Foundation.

Funding Information:
The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry. We would like to acknowledge PALGA (Dutch Pathology Registry) for providing data and collection of specimens. We would like to acknowledge the NCI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NCI-AVL Biobank material and lab support. We also thank the Sacha Swarttouw Stichting for funding this study.

Funding Information:
The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry. We would like to acknowledge PALGA (Dutch Pathology Registry) for providing data and collection of specimens. We would like to acknowledge the NCI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NCI-AVL Biobank material and lab support. We also thank the Sacha Swarttouw Stichting for funding this study.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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