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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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 |
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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 |
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