Abstract PO-084: Genetic profiling of rat gliomas and cardiac schwannomas from cell phone radiofrequency radiation exposure using a targeted next-generation sequencing gene panel

Abstract

The cancer hazard associated with exposure to cell phone radiofrequency radiation (RFR) was examined using lifetime exposure in Sprague-Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas in the brain and schwannomas in the heart. In order to understand the translational relevance of these rat tumors for human disease, we examined the top 23 orthologous cancer genes mutated in human gliomas using a custom built a next-generation sequencing gene panel for rats based on Illumina’s TruSeq Custom Amplicon Technology. SD rat tissues (gliomas =15; cardiac schwannomas=9, interim (1 year) sacrificed non-tumor brain tissues from RFR exposed rats =30, control brain and heart control tissues from lifetime exposure=10 each, and age-matched control brain tissues from interim sacrificed rats=10) from the RI-RFR cancer bioassay were examined in this study. The deepSNV R-package with various filtering criteria and the read depth of >1000x were used to identify single-nucleotide variants (SNVs) in the rat gliomas and schwannomas. At 5% allelic frequency, there were an average of 43 SNVs per rat glioma and point mutations were detected in 9 genes (Arid1a, Cic, Tert promoter, Tp53, Atrx, Nf1, Pdgfra, Pi3kr1, and Setd2) in at least 3 or more rat gliomas based on population frequency. Five genes (Nf1, Tert promoter, Setd2, Arid1a, and Pdgfra) harbored SNVs in interim sacrificed brain tissues that were also present in RFR-exposed gliomas from lifetime exposure. Interestingly, no mutations were detected in hotspot regions of Idh1, Idh2, Egfr or Braf. In contrast to most human gliomas which harbor mutations in IDH1 and IDH2 genes, the rat gliomas seem to be Idh1 wild type with mutations in the other glioma-related genes. Primary cardiac tumors are extremely rare in humans. With this targeted NGS panel (at allelic frequency of 2.5%), there were an average of 146 SNVs per rat cardiac schwannoma and unique point mutations were detected in Cic, Egfr, Arid1a, Nf1, Setd2, Cdkn2a, Erbb2, Atrx, Pdgfra, and Notch1 in 3 or more cardiac schwannomas. A subset of the SNVs (Arid1a, Tp53, and Nf1) in rat gliomas was confirmed in human gliomas in the COSMIC database supporting the translational relevance of the rat gliomas for human disease. In addition, several SNVs from rat gliomas and cardiac schwannomas were found in various human cancers including carcinomas, hematopoietic neoplasms, melanomas and neuroendocrine tumors. In conclusion, the rat gliomas appear to share genetic alterations with a subtype of IDH1 wildtype human gliomas and rat primary cardiac schwannomas also harbor mutations in some of the queried cancer genes. Citation Format: Ramesh C. Kovi, Andrea Vornoli, Ashley Brooks, Thai Vu T. Ton, Miaofei Xu, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Fiorella Belpoggi, Arun R. Pandiri. Genetic profiling of rat gliomas and cardiac schwannomas from cell phone radiofrequency radiation exposure using a targeted next-generation sequencing gene panel [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-084.