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Frequent PTPRK–RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma
Author(s) -
Sekine Shigeki,
Yamashita Satoshi,
Tanabe Taro,
Hashimoto Taiki,
Yoshida Hiroshi,
Taniguchi Hirokazu,
Kojima Motohiro,
Shinmura Kazuya,
Saito Yutaka,
Hiraoka Nobuyoshi,
Ushijima Toshikazu,
Ochiai Atsushi
Publication year - 2016
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4709
Subject(s) - hyperplastic polyp , wnt signaling pathway , kras , cancer research , colorectal cancer , immunohistochemistry , mutation , biology , medicine , pathology , genetics , cancer , gene , colonoscopy
The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next‐generation sequencing and reverse transcription‐PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK–RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β‐catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK–RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.