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Journal Articles Journal of Pathology Year : 2022

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

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Franck TIRODE
Patricia Berthon
Richard Wild
  • Function : Author
Agnes Neuville
  • Function : Author
Helene Bonte
  • Function : Author
Isabelle Moulonguet
  • Function : Author
Françoise Plantier
  • Function : Author
Frantz Dupuy
  • Function : Author
Alexiane Dallot
  • Function : Author
Alice Seris
  • Function : Author

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 (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 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 case, 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.
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hal-03713520 , version 1 (04-07-2022)

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Thibault Kervarrec, Daniel Pissaloux, Jeremie Poilane, Franck TIRODE, Anne Tallet, et al.. Recurrent FOXK1 :: GRHL and GPS2 :: GRHL fusions in trichogerminoma. Journal of Pathology, 2022, 257 (1), pp.96-108. ⟨10.1002/path.5872⟩. ⟨hal-03713520⟩
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