Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.

Cappellesso, R., Nozzoli, F., Zito Marino, F., Simi, S., Castiglione, F., De Giorgi, V., et al. (2021). NTRK Gene Fusion Detection in Atypical Spitz Tumors. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(22), 12332-12332 [10.3390/ijms222212332].

NTRK Gene Fusion Detection in Atypical Spitz Tumors

Ricci, Costantino;
2021

Abstract

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.
2021
Cappellesso, R., Nozzoli, F., Zito Marino, F., Simi, S., Castiglione, F., De Giorgi, V., et al. (2021). NTRK Gene Fusion Detection in Atypical Spitz Tumors. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(22), 12332-12332 [10.3390/ijms222212332].
Cappellesso, Rocco; Nozzoli, Filippo; Zito Marino, Federica; Simi, Sara; Castiglione, Francesca; De Giorgi, Vincenzo; Cota, Carlo; Senetta, Rebecca; S...espandi
File in questo prodotto:
File Dimensione Formato  
NTRK Gene Fusion Detection in.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 3.42 MB
Formato Adobe PDF
3.42 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/902089
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 12
social impact