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Comprehensive characterization of RSPO fusions in colorectal traditional serrated adenomas
Author(s) -
Sekine Shigeki,
Ogawa Reiko,
Hashimoto Taiki,
Motohiro Kojima,
Yoshida Hiroshi,
Taniguchi Hirokazu,
Saito Yutaka,
Yasuhiro Ohno,
Ochiai Atsushi,
Hiraoka Nobuyoshi
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13265
Subject(s) - biology , wnt signaling pathway , fusion gene , cancer research , microbiology and biotechnology , gene , genetics
Aims Traditional serrated adenoma ( TSA ) is a rare but distinct type of colorectal polyp. Our previous study showed that PTPRK – RSPO 3 fusions are frequent and characteristic genetic alterations in TSA s. This study aimed to characterize comprehensively the prevalence and variability of RSPO fusions in colorectal TSA s. Methods and results We examined RSPO expression and explored novel RSPO fusions in 129 TSA s, including 66 lesions analysed previously for WNT pathway gene mutations. Quantitative polymerase chain reaction ( qPCR ) analyses identified three and 43 TSA s overexpressing RSPO 2 and RSPO 3 , respectively, whereas the expression of RSPO 1 and RSPO 4 was marginal or undetectable in all cases. RSPO overexpression was always mutually exclusive with other WNT pathway gene mutations. Known PTPRK – RSPO 3 fusions were detected in 37 TSA s, all but one of which overexpressed RSPO 3 . In addition, rapid amplification of cDNA ends revealed three novel RSPO fusion transcripts, an NRIP 1– RSPO 2 fusion and two PTPRK – RSPO 3 fusion isoforms, in six TSA s. Overall, 43 TSA s had RSPO fusions (33%), whereas four TSA s (3%) overexpressed RSPO in the absence of RSPO fusions. TSA s with RSPO fusions showed several clinicopathological features, including distal localization ( P = 0.0063), larger size ( P = 0.0055), prominent ectopic crypt foci ( P = 8.4 × 10 −4 ), association of a high‐grade component ( P = 1.1 × 10 −4 ), and the presence of KRAS mutations ( P = 4.5 × 10 −5 ). Conclusions The present study identified RSPO fusion transcripts, including three novel transcripts, in one‐third of colorectal TSA s and showed that PTPRK – RSPO 3 fusions were the predominant cause of RSPO overexpression in colorectal TSA .