Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

Fiche publication

Date publication

janvier 2022

Journal

The Journal of pathology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CRIBIER Bernard

Tous les auteurs :
Kervarrec T, Pissaloux D, Poilane J, Tirode F, Tallet A, Collin C, Tallegas M, Berthon P, Gaboriaud P, Sohier P, Calonje E, Luzar B, Goto K, Cokelaere K, Lamant L, Balme B, Wild R, Neuville A, Deschamps L, Auberger E, Paumier V, Bonte H, Moulonguet I, Plantier F, Cales V, Pinsolle V, Roblet D, Dupuy F, Dallot A, Seris A, Jouary T, Houben R, Schrama D, Hesbacher S, Macagno N, Battistella M, Cribier B, Vergier B, de la Fouchardière A, Jullie ML

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35049062

Résumé

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.