{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:10:33Z","timestamp":1792253433266,"version":"4.4.0"},"reference-count":47,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"796","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:p>Clones harboring cancer driver mutations can expand in normal tissues, known as somatic mosaicism, and can be influenced by age and environmental and germline factors. Somatic mosaicism in the blood predicts the risk of hematological malignancies; however, the relevance of somatic mosaicism to solid tumors remains unclear, in part because of limited sample availability. Lifestyle habits, including alcohol consumption and tobacco smoking, and pathogenic germline variants increase the risk of developing esophageal squamous cell carcinoma (ESCC). Because somatic mosaicism in the esophagus is known to be associated with aging and lifestyle habits and considering the contiguity of squamous epithelium from the esophagus to the oral cavity, we noninvasively collected buccal mucosa samples from patients with and without ESCC using swabs of different sizes and conducted deep error-corrected sequencing of 26 cancer driver genes to obtain comprehensive landscapes of tissue remodeling by driver-mutant clones. We found that the number of mutations increased with drinking, but only in individuals with germline risks. Moreover, across positively selected genes in the buccal mucosa, mutations increased with age and smoking regardless of germline risks, whereas drinking affected only those with germline risks. The buccal mucosa of patients with ESCC was extensively remodeled, and models predicting the presence of ESCC demonstrated high accuracy with smaller swab sizes, possibly because of their higher sensitivity in detecting small mutant clones. In conclusion, we showed that buccal mucosal remodeling reflects lifestyle and germline risks, as well as age, which might be exploited for noninvasive risk assessment of ESCC.<\/jats:p>","DOI":"10.1126\/scitranslmed.adq6740","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T22:02:49Z","timestamp":1746050569000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Somatic mosaicism in the buccal mucosa reflects lifestyle and germline risk factors for esophageal squamous cell carcinoma"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4636-5032","authenticated-orcid":true,"given":"Akira","family":"Yokoyama","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, 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