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Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report

Adenocarcinoma of the esophagus (EAC) and gastroesophageal junction (GEJ-AC) is associated with poor prognosis, treatment resistance and limited systemic therapeutic options. To deeply understand the genomic landscape of this cancer type, and potentially identify a therapeutic target in a neoadjuvan...

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Autores principales: Ferrari, Anna, Fiocca, Roberto, Bonora, Elena, Domizio, Chiara, Fonzi, Eugenio, Angeli, Davide, Domenico Raulli, Gian, Mattioli, Sandro, Martinelli, Giovanni, Molinari, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137952/
https://www.ncbi.nlm.nih.gov/pubmed/37107676
http://dx.doi.org/10.3390/genes14040918
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author Ferrari, Anna
Fiocca, Roberto
Bonora, Elena
Domizio, Chiara
Fonzi, Eugenio
Angeli, Davide
Domenico Raulli, Gian
Mattioli, Sandro
Martinelli, Giovanni
Molinari, Chiara
author_facet Ferrari, Anna
Fiocca, Roberto
Bonora, Elena
Domizio, Chiara
Fonzi, Eugenio
Angeli, Davide
Domenico Raulli, Gian
Mattioli, Sandro
Martinelli, Giovanni
Molinari, Chiara
author_sort Ferrari, Anna
collection PubMed
description Adenocarcinoma of the esophagus (EAC) and gastroesophageal junction (GEJ-AC) is associated with poor prognosis, treatment resistance and limited systemic therapeutic options. To deeply understand the genomic landscape of this cancer type, and potentially identify a therapeutic target in a neoadjuvant chemotherapy non-responder 48-year-old man, we adopted a multi-omic approach. We simultaneously evaluated gene rearrangements, mutations, copy number status, microsatellite instability and tumor mutation burden. The patient displayed pathogenic mutations of the TP53 and ATM genes and variants of uncertain significance of three kinases genes (ERBB3, CSNK1A1 and RPS6KB2), along with FGFR2 and KRAS high copy number amplification. Interestingly, transcriptomic analysis revealed the Musashi-2 (MSI2)-C17orf64 fusion that has never been reported before. Rearrangements of the RNA-binding protein MSI2 with a number of partner genes have been described across solid and hematological tumors. MSI2 regulates several biological processes involved in cancer initiation, development and resistance to treatment, and deserves further investigation as a potential therapeutic target. In conclusion, our extensive genomic characterization of a gastroesophageal tumor refractory to all therapeutic approaches led to the discovery of the MSI2-C17orf64 fusion. The results underlie the importance of deep molecular analyses enabling the identification of novel patient-specific markers to be monitored during therapy or even targeted at disease evolution.
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spelling pubmed-101379522023-04-28 Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report Ferrari, Anna Fiocca, Roberto Bonora, Elena Domizio, Chiara Fonzi, Eugenio Angeli, Davide Domenico Raulli, Gian Mattioli, Sandro Martinelli, Giovanni Molinari, Chiara Genes (Basel) Case Report Adenocarcinoma of the esophagus (EAC) and gastroesophageal junction (GEJ-AC) is associated with poor prognosis, treatment resistance and limited systemic therapeutic options. To deeply understand the genomic landscape of this cancer type, and potentially identify a therapeutic target in a neoadjuvant chemotherapy non-responder 48-year-old man, we adopted a multi-omic approach. We simultaneously evaluated gene rearrangements, mutations, copy number status, microsatellite instability and tumor mutation burden. The patient displayed pathogenic mutations of the TP53 and ATM genes and variants of uncertain significance of three kinases genes (ERBB3, CSNK1A1 and RPS6KB2), along with FGFR2 and KRAS high copy number amplification. Interestingly, transcriptomic analysis revealed the Musashi-2 (MSI2)-C17orf64 fusion that has never been reported before. Rearrangements of the RNA-binding protein MSI2 with a number of partner genes have been described across solid and hematological tumors. MSI2 regulates several biological processes involved in cancer initiation, development and resistance to treatment, and deserves further investigation as a potential therapeutic target. In conclusion, our extensive genomic characterization of a gastroesophageal tumor refractory to all therapeutic approaches led to the discovery of the MSI2-C17orf64 fusion. The results underlie the importance of deep molecular analyses enabling the identification of novel patient-specific markers to be monitored during therapy or even targeted at disease evolution. MDPI 2023-04-15 /pmc/articles/PMC10137952/ /pubmed/37107676 http://dx.doi.org/10.3390/genes14040918 Text en © 2023 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 Case Report
Ferrari, Anna
Fiocca, Roberto
Bonora, Elena
Domizio, Chiara
Fonzi, Eugenio
Angeli, Davide
Domenico Raulli, Gian
Mattioli, Sandro
Martinelli, Giovanni
Molinari, Chiara
Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title_full Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title_fullStr Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title_full_unstemmed Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title_short Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
title_sort detection of a novel msi2-c17orf64 transcript in a patient with aggressive adenocarcinoma of the gastroesophageal junction: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137952/
https://www.ncbi.nlm.nih.gov/pubmed/37107676
http://dx.doi.org/10.3390/genes14040918
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