Recurrent FOXK1 :: GRHL and GPS2 :: GRHL fusions in trichogerminoma
(1, 2)
,
(3, 4)
,
(1, 5)
,
(4)
,
(5)
,
(5)
,
(1)
,
(2)
,
(2)
,
(6, 7)
,
(8)
,
(9)
,
(10)
,
(11)
,
(12)
,
(13)
,
,
,
(14)
,
(15)
,
(16)
,
,
,
,
(17)
,
(18)
,
(19)
,
,
,
,
(17)
,
(20)
,
(20)
,
(20)
,
(3, 21)
,
(22)
,
(23)
,
(18)
,
(3, 4)
,
(18)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Thibault Kervarrec
- Function : Correspondent author
- PersonId : 1146345
- ORCID : 0000-0002-2201-6914
Daniel Pissaloux
- Function : relator_co_first_author
Franck TIRODE
- Function : Author
- PersonId : 1062896
- IdHAL : franck-tirode
- ORCID : 0000-0003-4731-7817
- IdRef : 161841147
Patricia Berthon
- Function : Author
- PersonId : 737332
- IdHAL : patricia-berthon
- ORCID : 0000-0002-3491-7613
- IdRef : 253130743
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
Maxime Battistella
- Function : Author
- PersonId : 770105
- ORCID : 0000-0002-7053-7431
Arnaud de La Fouchardiere
- Function : relator_co_last_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.