Two Faces of UV Mutagenesis: Independent and Collateral Mutagenesis in Skin Cancers
Abstract
Cutaneous melanoma and basal cell carcinoma (BCC) represent the two primary malignancies driven by solar ultraviolet (UV) radiation. To map the spatial topology and distance dependence of their mutational signatures, we deployed new analytical bioinformatics workflow utilizing two convergent strategies: a data-driven read-level phasing framework to discriminate between collateral mutational events versus independent ones and a hypothesis-driven spatial permutational simulation model to capture density-dependent local deviations. A whole-genome analysis employing this framework unexpectedly reveals two fundamentally distinct lesion-processing landscapes, present in both BCC and melanoma. While independent mutations consistently reproduce canonical UV signatures (SBS7a-c) in both tumor types, collateral mutations tell a distinct and more varied narrative between BCC and melanoma. These collateral mutations are unusually abundant for non-UV characteristics, such as agerelated SBS1 and SBS5, and display a notable 3′ to 5′ asymmetry near UV-induced lesions in pyrimidine dimers. We also demonstrated that BCC displays a pronounced enrichment of dinucleotide base substitutions flanking UV-signature sites on the 3′ side, particularly CA>TG and CG>TA changes. Ultimately, these topological patterns in both tumors indicate that a primary photoproduct seeds secondary mutagenesis within its local chromatin environment, dramatically altering our understanding of UV-induced lesion processing.
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BibTeX
@article{gunbin2026faces,
title = {{Two Faces of UV Mutagenesis: Independent and Collateral Mutagenesis in Skin Cancers}},
author = {Konstantin Gunbin and Zamart Ramazanova and Bakhyt Matkarimov and Murat Saparbaev and Sergey Nikolaev and Andrey Yurchenko},
journal = {Life},
year = {2026},
month = aug,
doi = {10.3390/life16081300},
url = {https://hal.science/hal-05740317v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Two Faces of UV Mutagenesis: Independent and Collateral Mutagenesis in Skin Cancers
AU - Konstantin Gunbin
AU - Zamart Ramazanova
AU - Bakhyt Matkarimov
AU - Murat Saparbaev
AU - Sergey Nikolaev
AU - Andrey Yurchenko
PY - 2026
DA - 2026/08/07
JO - Life
DO - 10.3390/life16081300
UR - https://hal.science/hal-05740317v1
AB - Cutaneous melanoma and basal cell carcinoma (BCC) represent the two primary malignancies driven by solar ultraviolet (UV) radiation. To map the spatial topology and distance dependence of their mutational signatures, we deployed new analytical bioinformatics workflow utilizing two convergent strategies: a data-driven read-level phasing framework to discriminate between collateral mutational events versus independent ones and a hypothesis-driven spatial permutational simulation model to capture density-dependent local deviations. A whole-genome analysis employing this framework unexpectedly reveals two fundamentally distinct lesion-processing landscapes, present in both BCC and melanoma. While independent mutations consistently reproduce canonical UV signatures (SBS7a-c) in both tumor types, collateral mutations tell a distinct and more varied narrative between BCC and melanoma. These collateral mutations are unusually abundant for non-UV characteristics, such as agerelated SBS1 and SBS5, and display a notable 3′ to 5′ asymmetry near UV-induced lesions in pyrimidine dimers. We also demonstrated that BCC displays a pronounced enrichment of dinucleotide base substitutions flanking UV-signature sites on the 3′ side, particularly CA>TG and CG>TA changes. Ultimately, these topological patterns in both tumors indicate that a primary photoproduct seeds secondary mutagenesis within its local chromatin environment, dramatically altering our understanding of UV-induced lesion processing.
SN - 2075-1729
ER -