Abstract 3414: Novel MGMT variant association in Mexican patients with astrocytoma

Abstract

Abstract Introduction: Astrocytomas are the most common and lethal brain tumors with a median survival of 15 months. Different biomarkers have arisen to classify and treat this type of tumors; one of these markers is MGMT. The methylation status of this gene is a prognostic and predictive factor. The MGMT (O-6-Methylguanine-DNA Methyltransferase) is involved in the cellular response to the effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. The dysregulation of this methylation is critical in the development of certain cancers. Objective: To identify germinal MGMT gene variations in patients with astrocytoma. Material and methods: 55 randomly selected Mexican patients diagnosed with astrocytoma between 2008-2014 were consented to perform the molecular analysis of the whole gene and 5´UTR and 3´UTR regions of MGMT at Ion Torrent platform. Each amplified region had a depth of minimum 1500x. Ion Reporter software was used to analyze the genetic variants and using Integrative Genomic Viewer we confirmed that each variant had a Phred higher than 25. Genotypic frequencies were compared with HapMapMex and Mexican ancestry population from the 1000 Genomes project. Results. In lymphocytes DNA, eight genetic variants were found, and two of them were statistically significant risk factors: rs7896488 alternative allele A with a frequency of 15% in patients with astrocytoma, and only 4% of the control group (OR=5.53, IC 1.96-15.59 p = 0.0007) and rs2308326 ancestral allele C, where 93% of the patients were carriers of allele C in contrast with 73% of controls (OR=5.39, IC 2.29-12.69 p = 0.000019). These variants are non-coding single nucleotide polymorphisms, rs7896488 is a 3' UTR genetic variant, while rs2308326 is an intronic variant. Conclusion: Our study found two new risk SNV for Astrocytoma in a Mexican population. Citation Format: Liliana Gomez-Flores-Ramos, Talia Wegman-Ostrosky. Novel MGMT variant association in Mexican patients with astrocytoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2017-3414