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Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients

Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) or platelet derived growth factor receptor α (PDGFRA) genes. However, whether genotype analysis should be regarded...

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Autores principales: Liang, Li, Li, Xin, Li, Dong, Liu, Ping, Nong, Lin, Dong, Ying, Liu, Jumei, Huang, Sixia, Li, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798044/
https://www.ncbi.nlm.nih.gov/pubmed/33552291
http://dx.doi.org/10.3892/ol.2021.12435
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author Liang, Li
Li, Xin
Li, Dong
Liu, Ping
Nong, Lin
Dong, Ying
Liu, Jumei
Huang, Sixia
Li, Ting
author_facet Liang, Li
Li, Xin
Li, Dong
Liu, Ping
Nong, Lin
Dong, Ying
Liu, Jumei
Huang, Sixia
Li, Ting
author_sort Liang, Li
collection PubMed
description Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) or platelet derived growth factor receptor α (PDGFRA) genes. However, whether genotype analysis should be regarded as a prognostic indicator remains unclear. In the present study, clinicopathological data and the mutation phenotypes of KIT and PDGFRA genes were assessed in a series of 302 patients with GISTs at a single center. Univariate and multivariate Cox regression analyses were performed to identify the clinicopathological and mutational factors associated with relapse-free survival (RFS) in patients who had undergone complete primary GIST resection. KIT and PDGFRA mutations were identified in 233 (77.2%) and 30 (9.9%) cases, respectively. The following clinicopathological parameters were significantly associated with a shorter RFS: Male, non-gastric tumor origin, larger tumor size (>5 cm), high mitotic activity (>5/50 high-power fields), necrosis and epithelioid morphology. Tumors at non-gastric sites, with high National Institutes of Health risk classification, high World Health Organization (WHO) grade and KIT deletion involving codons 557/558/559 exhibited a significantly higher risk of progression. In the Cox regression model, KIT deletion involving codons 557/558/559, non-gastric origin and high WHO grade were independent indicators of RFS. The adverse prognosis associated with KIT deletions involving codons 557/558/559 was also observed for gastric GISTs. Conversely, spindle morphology, KIT exon 11 substitution and PDGFRA exon 18 mutation were associated with a longer RFS and lower rate of relapse. Furthermore, the coexistence of KIT exon 11 deletion and exon 13 duplication was observed in one tumor, with adverse prognostic features. Heterogeneity affecting morphology, immunostaining and genotype was identified in 4 cases. In addition, the presence of succinate dehydrogenase-deficient GIST was found in 5 cases (3.6%). In conclusion, the tumor genotype with regard to KIT and PDGFRA mutations exhibited prognostic significance for the risk of GIST progression and may be helpful for the optimization of tailored adjuvant therapy.
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spelling pubmed-77980442021-02-04 Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients Liang, Li Li, Xin Li, Dong Liu, Ping Nong, Lin Dong, Ying Liu, Jumei Huang, Sixia Li, Ting Oncol Lett Articles Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) or platelet derived growth factor receptor α (PDGFRA) genes. However, whether genotype analysis should be regarded as a prognostic indicator remains unclear. In the present study, clinicopathological data and the mutation phenotypes of KIT and PDGFRA genes were assessed in a series of 302 patients with GISTs at a single center. Univariate and multivariate Cox regression analyses were performed to identify the clinicopathological and mutational factors associated with relapse-free survival (RFS) in patients who had undergone complete primary GIST resection. KIT and PDGFRA mutations were identified in 233 (77.2%) and 30 (9.9%) cases, respectively. The following clinicopathological parameters were significantly associated with a shorter RFS: Male, non-gastric tumor origin, larger tumor size (>5 cm), high mitotic activity (>5/50 high-power fields), necrosis and epithelioid morphology. Tumors at non-gastric sites, with high National Institutes of Health risk classification, high World Health Organization (WHO) grade and KIT deletion involving codons 557/558/559 exhibited a significantly higher risk of progression. In the Cox regression model, KIT deletion involving codons 557/558/559, non-gastric origin and high WHO grade were independent indicators of RFS. The adverse prognosis associated with KIT deletions involving codons 557/558/559 was also observed for gastric GISTs. Conversely, spindle morphology, KIT exon 11 substitution and PDGFRA exon 18 mutation were associated with a longer RFS and lower rate of relapse. Furthermore, the coexistence of KIT exon 11 deletion and exon 13 duplication was observed in one tumor, with adverse prognostic features. Heterogeneity affecting morphology, immunostaining and genotype was identified in 4 cases. In addition, the presence of succinate dehydrogenase-deficient GIST was found in 5 cases (3.6%). In conclusion, the tumor genotype with regard to KIT and PDGFRA mutations exhibited prognostic significance for the risk of GIST progression and may be helpful for the optimization of tailored adjuvant therapy. D.A. Spandidos 2021-02 2021-01-04 /pmc/articles/PMC7798044/ /pubmed/33552291 http://dx.doi.org/10.3892/ol.2021.12435 Text en Copyright: © Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Liang, Li
Li, Xin
Li, Dong
Liu, Ping
Nong, Lin
Dong, Ying
Liu, Jumei
Huang, Sixia
Li, Ting
Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title_full Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title_fullStr Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title_full_unstemmed Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title_short Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients
title_sort mutational characteristics of gastrointestinal stromal tumors: a single-center analysis of 302 patients
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798044/
https://www.ncbi.nlm.nih.gov/pubmed/33552291
http://dx.doi.org/10.3892/ol.2021.12435
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