{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:41Z","timestamp":1785437921660,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR070026"],"award-info":[{"award-number":["RS-2022-NR070026"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2022-NR070026"],"award-info":[{"award-number":["RS-2022-NR070026"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Korea government"},{"name":"Yeouido St. Mary\u2019s Hospital"},{"id":[{"id":"https:\/\/ror.org\/0229xaa13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: How the histologically benign tier of lung preinvasive lesions\u2014atypical adenomatous hyperplasia (AAH) and squamous dysplasia (SD)\u2014relates genomically to its paired carcinoma is unclear. To identify early versus late events, we compared synchronous preinvasive and invasive lesions from the same patient. Methods: Whole-exome sequencing was performed on 33 FFPE samples from 11 patients (7 AAH\u2013lung adenocarcinoma [LUAD] and 4 SD\u2013squamous cell carcinoma [SqCC] pairs, with paired normal lung). FFPE artefacts were mitigated by paired-normal subtraction, panel-of-normals filtering, and orthogonal caller cross-validation. Cancer-panel variants were classified as cancer-only, shared, or preinvasive-only. Results: Only \u223c10% of cancer-panel variants were shared between paired lesions (\u223c50% carcinoma-only, \u223c40% preinvasive-only), indicating that benign AAH\/SD do not broadly mirror the paired carcinoma. Within this small shared fraction, the early-driver pattern diverged between tracks: AAH\u2013LUAD pairs tended to share EGFR alterations, whereas the four SD\u2013SqCC pairs featured MET-pathway alterations without any shared EGFR events. TP53 and most other canonical drivers were carcinoma-confined (within-cohort contrast direction-consistent but non-significant); three patients lacked any canonical driver despite substantial mutational burden. Conclusions: In this pilot cohort, benign AAH and SD were genomically largely distinct from their paired carcinomas, sharing only a small set of key drivers whose identity diverged between glandular and squamous tracks. This suggests that benign-appearing AAH\/SD differ from the more advanced AIS\/MIA precursors not only histologically but also at the genomic level. These hypothesis-generating findings require confirmation in larger, multi-omic cohorts.<\/jats:p>","DOI":"10.3390\/cancers18111691","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"1691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergent Genomic Drivers in Benign-Appearing Lung Precursors and Their Synchronous Carcinomas"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-9561","authenticated-orcid":false,"given":"Jieun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Hospital Pathology, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-7303","authenticated-orcid":false,"given":"Yuchae","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence Convergence & Engineering, Open Cyber University of Korea, Seoul 02087, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9655-6678","authenticated-orcid":false,"given":"Seung Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Hospital Pathology, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1430-4978","authenticated-orcid":false,"given":"Ye Won","family":"Song","sequence":"additional","affiliation":[{"name":"College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongsun","family":"Jung","sequence":"additional","affiliation":[{"name":"Syntekabio, Genome Data Integration Center, 519, Techno World 2, No. 187, Yuseong-gu, Daejeon 34025, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Kwon","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Jo","family":"Sa","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-3681","authenticated-orcid":false,"given":"Tae-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Hospital Pathology, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"69","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J. 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