Identification and validation of a previously missed mutational signature in colorectal cancer
Nature Communications, cilt.17, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 17 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1038/s41467-026-76472-w
- Dergi Adı: Nature Communications
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, BIOSIS, Chemical Abstracts Core, EMBASE, Geobase, INSPEC, MEDLINE, Directory of Open Access Journals, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest)
- Orta Doğu Teknik Üniversitesi Adresli: Evet
Özet
Mutational signature analysis has enhanced our understanding of mutagenic processes. In a recent study, we analyzed 802 microsatellite-stable colorectal cancers (CRC) and identified a de novo signature, SBS_D, which was decomposed into SBS18. Here, we re-evaluate this decomposition and provide evidence that SBS_D represents a distinct mutational process from SBS18. Through an analysis of 2,616 CRCs across three independent cohorts, we demonstrate that SBS_D is consistently present, suggesting this signature may have been previously overlooked. We illustrate that the pattern of SBS_D better aligns with signatures associated with deficiencies in DNA repair, despite evidence that SBS_D is not driven by canonical defects in these DNA repair pathways. Overall, this study identifies a previously unrecognized mutational signature in DNA repair-proficient CRC and proposes that its etiology may be linked to DNA repair infidelity emerging late in tumor development. SBS_D has been submitted to the COSMIC database and provisionally designated as SBS111.