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Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors

Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionab...

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Autores principales: Indio, Valentina, Schipani, Angela, Nannini, Margherita, Urbini, Milena, Rizzo, Alessandro, De Leo, Antonio, Altimari, Annalisa, Di Scioscio, Valerio, Messelodi, Daria, Tarantino, Giuseppe, Astolfi, Annalisa, Pantaleo, Maria Abbondanza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961685/
https://www.ncbi.nlm.nih.gov/pubmed/33806389
http://dx.doi.org/10.3390/jcm10051057
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author Indio, Valentina
Schipani, Angela
Nannini, Margherita
Urbini, Milena
Rizzo, Alessandro
De Leo, Antonio
Altimari, Annalisa
Di Scioscio, Valerio
Messelodi, Daria
Tarantino, Giuseppe
Astolfi, Annalisa
Pantaleo, Maria Abbondanza
author_facet Indio, Valentina
Schipani, Angela
Nannini, Margherita
Urbini, Milena
Rizzo, Alessandro
De Leo, Antonio
Altimari, Annalisa
Di Scioscio, Valerio
Messelodi, Daria
Tarantino, Giuseppe
Astolfi, Annalisa
Pantaleo, Maria Abbondanza
author_sort Indio, Valentina
collection PubMed
description Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionable for a tailored therapy. Methods: We analyzed 36 GIST tumor samples, either from formalin-fixed, paraffin-embedded by microarray or from fresh frozen tissue by RNA-seq, retrospectively collected among KIT-mutant and SDH-deficient GISTs. Pathway analysis was performed to highlight enriched and depleted transcriptional signatures. Tumor microenvironment and immune profile were also evaluated. Results: SDH-deficient GISTs showed a distinct GEP with respect to KIT-mutant GISTs. In particular, SDH-deficient GISTs were characterized by an increased expression of neural markers and by the activation of fibroblast growth factor receptor signaling and several biological pathways related to invasion and tumor progression. Among them, hypoxia and epithelial-to-mesenchymal transition emerged as features shared with SDH-deficient pheochromocytoma/paraganglioma. In addition, the study of immune landscape revealed the depletion of tumor microenvironment and inflammation gene signatures. Conclusions: This study provides an update of GEP in SDH-deficient GISTs, highlighting differences and similarities compared to KIT-mutant GISTs and to other neoplasm carrying the SDH loss of function. Our findings add a piece of knowledge in SDH-deficient GISTs, shedding light on their putative histology and on the dysregulated biological processes as targets of new therapeutic strategies.
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spelling pubmed-79616852021-03-17 Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors Indio, Valentina Schipani, Angela Nannini, Margherita Urbini, Milena Rizzo, Alessandro De Leo, Antonio Altimari, Annalisa Di Scioscio, Valerio Messelodi, Daria Tarantino, Giuseppe Astolfi, Annalisa Pantaleo, Maria Abbondanza J Clin Med Article Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionable for a tailored therapy. Methods: We analyzed 36 GIST tumor samples, either from formalin-fixed, paraffin-embedded by microarray or from fresh frozen tissue by RNA-seq, retrospectively collected among KIT-mutant and SDH-deficient GISTs. Pathway analysis was performed to highlight enriched and depleted transcriptional signatures. Tumor microenvironment and immune profile were also evaluated. Results: SDH-deficient GISTs showed a distinct GEP with respect to KIT-mutant GISTs. In particular, SDH-deficient GISTs were characterized by an increased expression of neural markers and by the activation of fibroblast growth factor receptor signaling and several biological pathways related to invasion and tumor progression. Among them, hypoxia and epithelial-to-mesenchymal transition emerged as features shared with SDH-deficient pheochromocytoma/paraganglioma. In addition, the study of immune landscape revealed the depletion of tumor microenvironment and inflammation gene signatures. Conclusions: This study provides an update of GEP in SDH-deficient GISTs, highlighting differences and similarities compared to KIT-mutant GISTs and to other neoplasm carrying the SDH loss of function. Our findings add a piece of knowledge in SDH-deficient GISTs, shedding light on their putative histology and on the dysregulated biological processes as targets of new therapeutic strategies. MDPI 2021-03-04 /pmc/articles/PMC7961685/ /pubmed/33806389 http://dx.doi.org/10.3390/jcm10051057 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Indio, Valentina
Schipani, Angela
Nannini, Margherita
Urbini, Milena
Rizzo, Alessandro
De Leo, Antonio
Altimari, Annalisa
Di Scioscio, Valerio
Messelodi, Daria
Tarantino, Giuseppe
Astolfi, Annalisa
Pantaleo, Maria Abbondanza
Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title_full Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title_fullStr Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title_full_unstemmed Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title_short Gene Expression Landscape of SDH-Deficient Gastrointestinal Stromal Tumors
title_sort gene expression landscape of sdh-deficient gastrointestinal stromal tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961685/
https://www.ncbi.nlm.nih.gov/pubmed/33806389
http://dx.doi.org/10.3390/jcm10051057
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