TY  - JOUR
T1  - Mutational signatures of environmental carcinogens in human tissue organoids revealed by duplex sequencing
AU  - Kucab, Jill E.
AU  - Nandi, Shuvro P.
AU  - Al-Serori, Halh
AU  - Dunstone, Ellie
AU  - Beck, Rebekah S.S.
AU  - Caipa Garcia, Angela L.
AU  - Wilde, Eleanor C.
AU  - Saeed, Safa
AU  - Francies, Hayley
AU  - Garnett, Mathew J.
AU  - Fu, Beiyuan
AU  - Yang, Fengtang
AU  - Saeb-Parsy, Kourosh
AU  - Huch, Meritxell
AU  - Drost, Jarno
AU  - Zilbauer, Matthias
AU  - Humphreys, Laura
AU  - Kisby, Glen
AU  - Arlt, Volker M.
AU  - Stratton, Michael R.
AU  - Alexandrov, Ludmil B.
AU  - Phillips, David H.
Y1  - 2026/06/23
PY  - 2026
N1  - doi: 10.1016/j.celrep.2026.117406
DO  - 10.1016/j.celrep.2026.117406
T2  - Cell Reports
JF  - Cell Reports
VL  - 45
IS  - 6
PB  - Elsevier
N2  - Environmental exposures play a pivotal role in carcinogenesis, yet their molecular imprints in human tissues remain incompletely understood. Here, we present an extensive catalog of mutational signatures induced by a panel of environmental carcinogens using human tissue-derived organoids coupled with high-fidelity duplex sequencing (NanoSeq). This unique combination enables direct detection of mutations without clonal expansion and reveals consistent carcinogen-specific signatures across multiple organ types (i.e., colon, stomach, liver, kidney, and pancreas). We identify mutational signatures for agents such as benzo[a]pyrene, aflatoxin B1, aristolochic acid I, and alkylating agents, some of which show strong concordance with known tumor signatures (e.g., SBS4, SBS11, SBS22, and SBS24) and previous experimentally-derived signatures. Our findings validate organoid models as physiologically relevant platforms for chemical mutagenesis and provide a foundational resource for decoding the environmental origins of human cancer.
AB  - Environmental exposures play a pivotal role in carcinogenesis, yet their molecular imprints in human tissues remain incompletely understood. Here, we present an extensive catalog of mutational signatures induced by a panel of environmental carcinogens using human tissue-derived organoids coupled with high-fidelity duplex sequencing (NanoSeq). This unique combination enables direct detection of mutations without clonal expansion and reveals consistent carcinogen-specific signatures across multiple organ types (i.e., colon, stomach, liver, kidney, and pancreas). We identify mutational signatures for agents such as benzo[a]pyrene, aflatoxin B1, aristolochic acid I, and alkylating agents, some of which show strong concordance with known tumor signatures (e.g., SBS4, SBS11, SBS22, and SBS24) and previous experimentally-derived signatures. Our findings validate organoid models as physiologically relevant platforms for chemical mutagenesis and provide a foundational resource for decoding the environmental origins of human cancer.
SN  - 2211-1247
M3  - doi: 10.1016/j.celrep.2026.117406
UR  - https://doi.org/10.1016/j.celrep.2026.117406
Y2  - 2026/06/15