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PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1
Most of the gastrointestinal stromal tumors (GISTs) have gain-of-function mutations in the KIT gene, which can be used as a prognostic marker for the biological behavior of tumors, predictive marker for the response of tyrosine kinase inhibitors, and diagnostic marker. Researchers have focused on PD...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838738/ https://www.ncbi.nlm.nih.gov/pubmed/27178821 http://dx.doi.org/10.3727/096504016X14576297492418 |
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author | Baskin, Yasemin Kocal, Gizem Calibasi Kucukzeybek, Betul Bolat Akbarpour, Mahdi Kayacik, Nurcin Sagol, Ozgul Ellidokuz, Hulya Oztop, Ilhan |
author_facet | Baskin, Yasemin Kocal, Gizem Calibasi Kucukzeybek, Betul Bolat Akbarpour, Mahdi Kayacik, Nurcin Sagol, Ozgul Ellidokuz, Hulya Oztop, Ilhan |
author_sort | Baskin, Yasemin |
collection | PubMed |
description | Most of the gastrointestinal stromal tumors (GISTs) have gain-of-function mutations in the KIT gene, which can be used as a prognostic marker for the biological behavior of tumors, predictive marker for the response of tyrosine kinase inhibitors, and diagnostic marker. Researchers have focused on PDGFRA mutations because of both their prognostic and predictive potential and DOG1 positivity for diagnosis on GISTs. The aim of this study is to investigate the effect DOG1, PDGFRA, and KIT mutations on the prediction of the outcome for GIST management. Polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17 and PDGFRA gene exons 12 and 18 with the genomic DNA of 46 GIST patients, and amplicons were sequenced in both directions. Immunocytochemical stainings were done by using primary antibodies. Molecular analysis revealed that the KIT mutation was observed in 63% of all cases, while the PDGFRA mutation was observed in 23.9% of cases. Significant relationships were found between age and KIT mutation, tumor location and KIT mutations, and tumor location and PDGFRA mutations (p ≤ 0.05). DOG1 positivity was detected in 65.2% of all GISTs and DOG1-positive cells had a higher KIT mutation ratio than DOG1-negative cells (p ≤ 0.05). KIT gene exon 11 mutations in DOG1-positive cells was higher than DOG1-negative cells (p ≤ 0.05). Conversely, KIT gene exon 13 mutations were higher in DOG1-negative cells than DOG1-positive cells (p ≤ 0.05). In this study, KIT mutation frequency was found similar with the European population; conversely, PDGFRA mutation frequency was similar with an Asian-Chinese-based study. KIT/PDGFRA mutations and tumor location can be used for the prediction of tumor behavior and the management of disease in GISTs. DOG1 positivity might be a candidate marker to support KIT and PDGFRA mutations, due to the higher DOG1 positivity in KIT exon 11 mutant and stomach- and small intestine-localized GISTs. |
format | Online Article Text |
id | pubmed-7838738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78387382021-02-16 PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 Baskin, Yasemin Kocal, Gizem Calibasi Kucukzeybek, Betul Bolat Akbarpour, Mahdi Kayacik, Nurcin Sagol, Ozgul Ellidokuz, Hulya Oztop, Ilhan Oncol Res Article Most of the gastrointestinal stromal tumors (GISTs) have gain-of-function mutations in the KIT gene, which can be used as a prognostic marker for the biological behavior of tumors, predictive marker for the response of tyrosine kinase inhibitors, and diagnostic marker. Researchers have focused on PDGFRA mutations because of both their prognostic and predictive potential and DOG1 positivity for diagnosis on GISTs. The aim of this study is to investigate the effect DOG1, PDGFRA, and KIT mutations on the prediction of the outcome for GIST management. Polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17 and PDGFRA gene exons 12 and 18 with the genomic DNA of 46 GIST patients, and amplicons were sequenced in both directions. Immunocytochemical stainings were done by using primary antibodies. Molecular analysis revealed that the KIT mutation was observed in 63% of all cases, while the PDGFRA mutation was observed in 23.9% of cases. Significant relationships were found between age and KIT mutation, tumor location and KIT mutations, and tumor location and PDGFRA mutations (p ≤ 0.05). DOG1 positivity was detected in 65.2% of all GISTs and DOG1-positive cells had a higher KIT mutation ratio than DOG1-negative cells (p ≤ 0.05). KIT gene exon 11 mutations in DOG1-positive cells was higher than DOG1-negative cells (p ≤ 0.05). Conversely, KIT gene exon 13 mutations were higher in DOG1-negative cells than DOG1-positive cells (p ≤ 0.05). In this study, KIT mutation frequency was found similar with the European population; conversely, PDGFRA mutation frequency was similar with an Asian-Chinese-based study. KIT/PDGFRA mutations and tumor location can be used for the prediction of tumor behavior and the management of disease in GISTs. DOG1 positivity might be a candidate marker to support KIT and PDGFRA mutations, due to the higher DOG1 positivity in KIT exon 11 mutant and stomach- and small intestine-localized GISTs. Cognizant Communication Corporation 2016-05-11 /pmc/articles/PMC7838738/ /pubmed/27178821 http://dx.doi.org/10.3727/096504016X14576297492418 Text en Copyright © 2016 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Baskin, Yasemin Kocal, Gizem Calibasi Kucukzeybek, Betul Bolat Akbarpour, Mahdi Kayacik, Nurcin Sagol, Ozgul Ellidokuz, Hulya Oztop, Ilhan PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title |
PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title_full |
PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title_fullStr |
PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title_full_unstemmed |
PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title_short |
PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1 |
title_sort | pdgfra and kit mutation status and its association with clinicopathological properties, including dog1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838738/ https://www.ncbi.nlm.nih.gov/pubmed/27178821 http://dx.doi.org/10.3727/096504016X14576297492418 |
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