{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:12:12Z","timestamp":1788775932353,"version":"build-2803163510"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"publisher","award":["Z1AES103266"],"award-info":[{"award-number":["Z1AES103266"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Somatic mutations are inevitable in human genomes and can lead to cancer initiation and tumor progression. Although many mutagenic processes have been linked to cancer, their activities in normal tissues before malignant transformation remain poorly characterized. Here, we analyzed the mutation profiles of 10,625 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C\u2192T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We also identified a second clock-like motif, T\u2192C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Motifs associated with other environmental and chemical mutagens showed sporadic and tissue-specific mutagenesis. APOBEC-induced C\u2192T and C\u2192G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most tissues. Together, our analyses elucidated several cancer-associated mutagenic processes in normal tissues and provided a robust analytical framework for quantifying mutagenic activities from somatic mutation catalogs.<\/jats:p>","DOI":"10.1093\/narcan\/zcag024","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:17:31Z","timestamp":1788520651000},"source":"Crossref","is-referenced-by-count":0,"title":["Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-1822","authenticated-orcid":false,"given":"Safia Mahabub","family":"Sauty","sequence":"first","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Durham, NC 27709 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Chung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Durham, NC 27709 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-2576","authenticated-orcid":false,"given":"Leszek J","family":"Klimczak","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences , Durham, NC 27709 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8399-1836","authenticated-orcid":false,"given":"Dmitry A","family":"Gordenin","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Durham, 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