Open Access

ARTICLE

PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1

Yasemin Baskin^*†‡, Gizem Calibasi Kocal^‡§, Betul Bolat Kucukzeybek^¶, Mahdi Akbarpour^#, Nurcin Kayacik^**, Ozgul Sagol^††, Hulya Ellidokuz^†‡‡, Ilhan Oztop^§§

* Institute of Oncology, Department of Basic Oncology, Dokuz Eylul University, Izmir, Turkey
† Faculty of Medicine, Department of Medical Informatics and Biostatistics, Dokuz Eylul University, Izmir, Turkey
‡ Personalized Medicine and Pharmacogenomics/Genomics Research Centre-BIFAGEM, Dokuz Eylul University, Izmir, Turkey
§ Institute of Health Sciences, Department of Basic Oncology, Dokuz Eylul University, Izmir, Turkey
¶ Ataturk Training and Research Hospital, Department of Pathology, Izmir Katip Celebi University, Izmir, Turkey
# German Cancer Research Center, Division of Translational Oncology, Heidelberg, Germany
** Molecular Oncology Laboratory, Dokuz Eylul University Hospital, Izmir, Turkey
†† Faculty of Medicine, Department of Pathology, Dokuz Eylul University, Izmir, Turkey
‡‡ Institute of Oncology, Department of Preventive Oncology, Dokuz Eylul University, Izmir, Turkey
§§ Faculty of Medicine, Department of Medical Oncology, Dokuz Eylul University, Izmir, Turkey

Oncology Research 2016, 24(1), 41-53. https://doi.org/10.3727/096504016X14576297492418

Abstract

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.

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