Combinational analysis of IDH1/IDH2 mutations, 1p/19q deletions and MGMT promoter methylation for molecular testing of glioma.

Authors

null

Xiaoni Zhang

HaploX Biotechnology, Shenzhen, China

Xiaoni Zhang , Hongyue Qu , Qing Yang , Ziyang Zhu , Tanxiao Huang , Shifu Chen , Jeremy Edwards , Mingyan Xu

Organizations

HaploX Biotechnology, Shenzhen, China, University of New Mexico, Albuquerque, NM

Research Funding

Pharmaceutical/Biotech Company

Background: Mutations in IDH1 and IDH2, co-deletion of 1p and 19q, and the hyper methylation of the MGMT promoter are the most reported genetic alterations in glioma tumors. Therefore, we designed a study to analyze the prevalence of these biomarkers in glioma, and the correlation of these biomarkers with diagnosis and prognosis. Methods: From September 2018 to January 2019, eighteen patients with primary glioma were prospectively enrolled. For each patient, freshly frozen tissue or FFPE samples were collected. DNA was extracted from these samples and sequenced to at least 5,000× coverage. IDH1/IDH2 mutations and 1p/19q deletions were detected from the sequencing data, whereas MGMT promoter methylation was evaluated by real-time fluorescence qPCR. Results: Of the eighteen patients, 44.4%(8/18) and 33.3%(6/18) harbored IDH1 /IDH2 mutations and 1p/19q deletions, respectively, and 72.2%(13/18) contained MGMT promoter hyper methylation. Within these patients, we found a correlation between IDH1/IDH2 mutation and 1p/19q deletion. Namely, among the 8 patients with a IDH1/IDH2 mutation, 75%(6/8) also contained a 1p/19q deletion, whereas none of the 10 patients with wide-type IDH1/IDH2 displayed the 1p/19q deletion. There was also a correlation between mutations at the loci and MGMT promoter hyper-methylation, specifically, 87.5%(7/8) of the patients with IDH1/IDH2 mutations also exhibited hyper-methylation in MGMT, whereas only hyper-methylation was observed in only 40% (4/10) of IDH1/IDH2 negative patients. Conclusions: From our preliminary result, IDH1/IDH2 mutations may be associated with 1p/19q deletion. To further verify this result, a larger, longitudinal study is ongoing at our institution.

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Cancer Prevention, Hereditary Genetics, and Epidemiology: Publication Only

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Germline Genetic Testing

Citation

J Clin Oncol 37, 2019 (suppl; abstr e13152)

DOI

10.1200/JCO.2019.37.15_suppl.e13152

Abstract #

e13152

Abstract Disclosures

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