Cargando…

NTRK Gene Fusion Detection in Atypical Spitz Tumors

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 wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Cappellesso, Rocco, Nozzoli, Filippo, Zito Marino, Federica, Simi, Sara, Castiglione, Francesca, De Giorgi, Vincenzo, Cota, Carlo, Senetta, Rebecca, Scognamiglio, Giosuè, Anniciello, Anna Maria, Cesinaro, Anna Maria, Mandalà, Mario, Gianatti, Andrea, Valente, Maria Gabriella, Valeri, Barbara, Sementa, Angela Rita, Ricci, Costantino, Corti, Barbara, Roviello, Giandomenico, Dei Tos, Angelo Paolo, Franco, Renato, Massi, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619835/
https://www.ncbi.nlm.nih.gov/pubmed/34830218
http://dx.doi.org/10.3390/ijms222212332
_version_ 1784605080935202816
author Cappellesso, Rocco
Nozzoli, Filippo
Zito Marino, Federica
Simi, Sara
Castiglione, Francesca
De Giorgi, Vincenzo
Cota, Carlo
Senetta, Rebecca
Scognamiglio, Giosuè
Anniciello, Anna Maria
Cesinaro, Anna Maria
Mandalà, Mario
Gianatti, Andrea
Valente, Maria Gabriella
Valeri, Barbara
Sementa, Angela Rita
Ricci, Costantino
Corti, Barbara
Roviello, Giandomenico
Dei Tos, Angelo Paolo
Franco, Renato
Massi, Daniela
author_facet Cappellesso, Rocco
Nozzoli, Filippo
Zito Marino, Federica
Simi, Sara
Castiglione, Francesca
De Giorgi, Vincenzo
Cota, Carlo
Senetta, Rebecca
Scognamiglio, Giosuè
Anniciello, Anna Maria
Cesinaro, Anna Maria
Mandalà, Mario
Gianatti, Andrea
Valente, Maria Gabriella
Valeri, Barbara
Sementa, Angela Rita
Ricci, Costantino
Corti, Barbara
Roviello, Giandomenico
Dei Tos, Angelo Paolo
Franco, Renato
Massi, Daniela
author_sort Cappellesso, Rocco
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8619835
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86198352021-11-27 NTRK Gene Fusion Detection in Atypical Spitz Tumors Cappellesso, Rocco Nozzoli, Filippo Zito Marino, Federica Simi, Sara Castiglione, Francesca De Giorgi, Vincenzo Cota, Carlo Senetta, Rebecca Scognamiglio, Giosuè Anniciello, Anna Maria Cesinaro, Anna Maria Mandalà, Mario Gianatti, Andrea Valente, Maria Gabriella Valeri, Barbara Sementa, Angela Rita Ricci, Costantino Corti, Barbara Roviello, Giandomenico Dei Tos, Angelo Paolo Franco, Renato Massi, Daniela Int J Mol Sci Article 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. MDPI 2021-11-15 /pmc/articles/PMC8619835/ /pubmed/34830218 http://dx.doi.org/10.3390/ijms222212332 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cappellesso, Rocco
Nozzoli, Filippo
Zito Marino, Federica
Simi, Sara
Castiglione, Francesca
De Giorgi, Vincenzo
Cota, Carlo
Senetta, Rebecca
Scognamiglio, Giosuè
Anniciello, Anna Maria
Cesinaro, Anna Maria
Mandalà, Mario
Gianatti, Andrea
Valente, Maria Gabriella
Valeri, Barbara
Sementa, Angela Rita
Ricci, Costantino
Corti, Barbara
Roviello, Giandomenico
Dei Tos, Angelo Paolo
Franco, Renato
Massi, Daniela
NTRK Gene Fusion Detection in Atypical Spitz Tumors
title NTRK Gene Fusion Detection in Atypical Spitz Tumors
title_full NTRK Gene Fusion Detection in Atypical Spitz Tumors
title_fullStr NTRK Gene Fusion Detection in Atypical Spitz Tumors
title_full_unstemmed NTRK Gene Fusion Detection in Atypical Spitz Tumors
title_short NTRK Gene Fusion Detection in Atypical Spitz Tumors
title_sort ntrk gene fusion detection in atypical spitz tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619835/
https://www.ncbi.nlm.nih.gov/pubmed/34830218
http://dx.doi.org/10.3390/ijms222212332
work_keys_str_mv AT cappellessorocco ntrkgenefusiondetectioninatypicalspitztumors
AT nozzolifilippo ntrkgenefusiondetectioninatypicalspitztumors
AT zitomarinofederica ntrkgenefusiondetectioninatypicalspitztumors
AT simisara ntrkgenefusiondetectioninatypicalspitztumors
AT castiglionefrancesca ntrkgenefusiondetectioninatypicalspitztumors
AT degiorgivincenzo ntrkgenefusiondetectioninatypicalspitztumors
AT cotacarlo ntrkgenefusiondetectioninatypicalspitztumors
AT senettarebecca ntrkgenefusiondetectioninatypicalspitztumors
AT scognamigliogiosue ntrkgenefusiondetectioninatypicalspitztumors
AT annicielloannamaria ntrkgenefusiondetectioninatypicalspitztumors
AT cesinaroannamaria ntrkgenefusiondetectioninatypicalspitztumors
AT mandalamario ntrkgenefusiondetectioninatypicalspitztumors
AT gianattiandrea ntrkgenefusiondetectioninatypicalspitztumors
AT valentemariagabriella ntrkgenefusiondetectioninatypicalspitztumors
AT valeribarbara ntrkgenefusiondetectioninatypicalspitztumors
AT sementaangelarita ntrkgenefusiondetectioninatypicalspitztumors
AT riccicostantino ntrkgenefusiondetectioninatypicalspitztumors
AT cortibarbara ntrkgenefusiondetectioninatypicalspitztumors
AT roviellogiandomenico ntrkgenefusiondetectioninatypicalspitztumors
AT deitosangelopaolo ntrkgenefusiondetectioninatypicalspitztumors
AT francorenato ntrkgenefusiondetectioninatypicalspitztumors
AT massidaniela ntrkgenefusiondetectioninatypicalspitztumors