Avtor/Urednik		Kervarrec, Thibault; Pissaloux, Daniel; Poilane, Jeremie; Tirode, Franck; Tallet, Anne; Collin, Christine; Tallegas, Matthias; Berthon, Patricia; Gaboriaud, Pauline; Luzar, Boštjan
Naslov		Recurrent FOXK1
Tip		članek
Leto izdaje		2022
Obseg		str. str.
ISSN		0022-3417 - The Journal of pathology
Jezik		eng
Abstrakt		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.
Proste vsebinske oznake		trichogerminoma trichoblastoma fusion transcript trihogerminom trihoblastom fuzijski prepis