Author/Editor		Kervarrec, Thibault; Pissaloux, Daniel; Poilane, Jeremie; Tirode, Franck; Tallet, Anne; Collin, Christine; Tallegas, Matthias; Berthon, Patricia; Gaboriaud, Pauline; Luzar, Boštjan
Title		Recurrent FOXK1
Type		članek
Publication year		2022
Volume		str. str.
ISSN		0022-3417 - The Journal of pathology
Language		eng
Abstract		We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests, ("cell balls") was present. Immunohistochemistry demonstrated the expression of cytokeratins (CK) 15, 17 and PHLDA1. In addition, numerous Cytokeratin 20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in 3 cases and a FOXK1::GRHL2 fusion in 2 cases. In a second series for validation (n=88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an 12 additional trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n= 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. This article is protected by copyright. All rights reserved.
Keywords		trichogerminoma trichoblastoma fusion transcript trihogerminom trihoblastom fuzijski prepis