EGFRvIII expression and isocitrate dehydrogenase mutations in patients with glioma

Taher,Mohiuddin M.; Dairi,Ghida; Butt,Ejaz Muhammad; Al‑Quthami,Khalid; Al‑Khalidi,Hisham; Jastania,Raid A.; Nageeti,Tahani H.; Bogari,Neda M.; Athar,Mohammad; Al‑Allaf,Faisal A.; Valerie,Kristoffer

doi:10.3892/ol.2020.12247

EGFRvIII expression and isocitrate dehydrogenase mutations in patients with glioma

Authors:
- Mohiuddin M. Taher
- Ghida Dairi
- Ejaz Muhammad Butt
- Khalid Al‑Quthami
- Hisham Al‑Khalidi
- Raid A. Jastania
- Tahani H. Nageeti
- Neda M. Bogari
- Mohammad Athar
- Faisal A. Al‑Allaf
- Kristoffer Valerie
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Affiliations: Medical Genetics Department, College of Medicine, Umm‑Al‑Qura University, Makkah 24381, Saudi Arabia, Medicine and Medical Sciences Research, Umm‑Al‑Qura University, Makkah 24381, Saudi Arabia, Department of Laboratory Medicine and Histopathology Division, Al‑Noor Specialty Hospital, Makkah 24242, Saudi Arabia, Department of Pathology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia, Department of Pathology, College of Medicine, Umm‑Al‑Qura University, Makkah 24381, Saudi Arabia, Radiation Oncology Department, King Abdullah Medical City, Makkah 24246, Saudi Arabia, Department of Radiation Oncology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
Published online on: October 23, 2020 https://doi.org/10.3892/ol.2020.12247
Article Number: 384
Copyright: © Taher et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Molecular pathology and personalized medicine are still being evolved in Saudi Arabia, and genetic testing for the detection of mutations as cancer markers have not been established in the diagnostics laboratories in Saudi Arabia. The aim of the present study was to determine the prevalence of isocitrate dehydrogenase (IDH1 and IDH2) mutations and epidermal growth factor receptor variant (EGFRv)III transcript expression in Saudi Arabian patients with glioma. Out of 117 brain tumors tested by reverse transcription‑quantitative PCR for EGFRvIII, 41 cases tested positive. In the glioblastoma (GBM) category, 28/55 tumors were positive, in astrocytoma tumors 5/22, and in oligodendrogliomas 4/13 cases were positive respectively. EGFRvIII transcript was sequenced by capillary electrophoresis to demonstrate the presence of EGFRvIII‑specific junction where exons 2‑7 were deleted. In the present study 106 tumors were sequenced for IDH1 exon‑4 mutations using the capillary sequencing method. The most common substitution missense mutation c.395G>A was found in 16 tumors. In the case of adamantinomatous craniopharyngioma, a novel missense mutation in c.472C>T was detected in IDH2 gene. Using next‑generation sequencing (NGS), 74 tumors were sequenced for the IDH1 gene, and a total of 8 missense variants were identified in 36 tumors in a population of Saudi Arabia. The missense mutation (c.395G>A) was detected in 29/36 of tumors. A novel intronic mutation in c.414+9T>A was found in 13 cases in the IDH1 gene. In addition, one case exhibited a novel synonymous mutation in c.369A>G. Eleven tumors were found to have compound mutations in the IDH1 gene. In IDH2 gene, out of a total of 16 variants found in 6 out of 45 tumors, nine were missense, five were synonymous and one was intronic. This is the first report from Saudi Arabian laboratories analyzing glioma tumors for EGFRvIII expression, and the first study from Saudi Arabia to analyze IDH mutations in gliomas using the capillary and NGS methods.

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