Double-base deletions and signatures associated with platinum adducts in metastatic cancer
- 1Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD , Rotterdam ,
Abstract
Platinum compounds preferably create intrastrand G-G adducts to halt replication in cancer cells. When successfully bypassed, resulting somatic variants end up in the genome. Unexpectedly, current double-base substitution signatures associated with platinum lack a GG component, and we hypothesized that deletion was missing from the possible solutions to circumvent a double-base lesion. We investigated a large pan-cancer metastatic cohort and generated platinum specific de novo double-base substitution and deletion (DBSD) signatures. One of the oxaliplatin associated DBSD signatures had GG deletion as dominant characteristic and also included new and known substitutions associated with platinum. Unforeseen among the additional results, DBSD signatures with deletion of TT as singular characteristic were strongly associated with microsatellite instability in multiple cohorts and provisionally in liquid biopsies. This study showed that DBSD signatures increase our understanding and cataloging of the effects caused by platinum and, in general, may aid in the discovery of new biological insights.
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BibTeX
@article{smid2026doublebase,
title = {{Double-base deletions and signatures associated with platinum adducts in metastatic cancer}},
author = {Marcel Smid and Lotte van Leeuwen and Saskia M Wilting and John W M Martens},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag945},
url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag945/8913150},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Double-base deletions and signatures associated with platinum adducts in metastatic cancer
AU - Marcel Smid
AU - Lotte van Leeuwen
AU - Saskia M Wilting
AU - John W M Martens
PY - 2026
DA - 2026/10/13
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag945
UR - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag945/8913150
AB - Platinum compounds preferably create intrastrand G-G adducts to halt replication in cancer cells. When successfully bypassed, resulting somatic variants end up in the genome. Unexpectedly, current double-base substitution signatures associated with platinum lack a GG component, and we hypothesized that deletion was missing from the possible solutions to circumvent a double-base lesion. We investigated a large pan-cancer metastatic cohort and generated platinum specific de novo double-base substitution and deletion (DBSD) signatures. One of the oxaliplatin associated DBSD signatures had GG deletion as dominant characteristic and also included new and known substitutions associated with platinum. Unforeseen among the additional results, DBSD signatures with deletion of TT as singular characteristic were strongly associated with microsatellite instability in multiple cohorts and provisionally in liquid biopsies. This study showed that DBSD signatures increase our understanding and cataloging of the effects caused by platinum and, in general, may aid in the discovery of new biological insights.
SN - 0305-1048
SN - 1362-4962
ER -