{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:11:11Z","timestamp":1780546271699,"version":"3.54.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>Colorectal carcinogenesis in familial adenomatous polyposis (FAP) follows a conventional adenoma-carcinoma sequence. However, previous studies have also reported the occurrence of traditional serrated adenomas (TSAs) in patients with FAP. In the present study, we analyzed the clinicopathologic and molecular features of 37 TSAs from 21 FAP patients. Histologically, the majority of FAP-associated TSAs showed typical cytology and slit-like serration; however, ectopic crypt formation was infrequent. Next-generation sequencing and Sanger sequencing identified <jats:italic toggle=\"yes\">KRAS<\/jats:italic> and <jats:italic toggle=\"yes\">BRAF<\/jats:italic> V600E mutations in 18 (49%) and 14 (38%) TSAs, respectively. Somatic <jats:italic toggle=\"yes\">APC<\/jats:italic> mutations were detected in 26 lesions (84% of analyzed cases). Three lesions had <jats:italic toggle=\"yes\">BRAF<\/jats:italic> non-V600E mutations, and 2 of them had a concurrent <jats:italic toggle=\"yes\">KRAS<\/jats:italic> mutation. Seven TSAs (19%) were associated with a precursor polyp, 6 with a hyperplastic polyp, and 1 with a sessile serrated lesion, and all of them showed the <jats:italic toggle=\"yes\">BRAF<\/jats:italic> V600E mutation. Additional sequencing analysis of 4 TSAs with a precursor polyp showed that the <jats:italic toggle=\"yes\">BRAF<\/jats:italic> V600E mutation was shared between the TSA and precursor components, but <jats:italic toggle=\"yes\">APC<\/jats:italic> mutations were exclusive to the TSA component in all the analyzed lesions. None of the lesions showed the high CpG island methylation phenotype. These results indicate that FAP-associated TSAs frequently have <jats:italic toggle=\"yes\">KRAS<\/jats:italic> or <jats:italic toggle=\"yes\">BRAF<\/jats:italic> mutations, similar to sporadic cases, and second-hit somatic <jats:italic toggle=\"yes\">APC<\/jats:italic> mutations are commonly involved in their tumorigenesis as in other FAP-associated tumors. Although progression to adenocarcinoma is likely rare, tumorigenesis via the serrated pathway occurs in patients with FAP.<\/jats:p>","DOI":"10.1097\/pas.0000000000001502","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:48:43Z","timestamp":1588970923000},"page":"1282-1289","source":"Crossref","is-referenced-by-count":5,"title":["Clinicopathologic and Molecular Characteristics of Familial Adenomatous Polyposis\u2013associated Traditional Serrated Adenoma"],"prefix":"10.1097","volume":"44","author":[{"given":"Takuma","family":"Okamura","sequence":"first","affiliation":[{"name":"Division of Diagnostic Pathology"},{"name":"Endoscopy Division, National Cancer Center Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Diagnostic 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