PDTM-07. DETECTION OF IDH1 R132H MOSAICISM IN ANAPLASTIC ASTROCYTOMA PATIENTS. (5th November 2018)

• Record Type: Journal Article
• Authors: Lee, Sulgi; Bornhorst, Miriam; Panditharatna, Eshini; Kambhampati, Madhuri; Nazarian, Javad
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi205
• Page End: vi205
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.849
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Anaplastic astrocytomas are aggressive cancers of glial cells that present poor prognosis and high recurrence. Heterozygous mutations in IDH1 and IDH2 genes are common in the patients with anaplastic astrocytomas and glioblastomas. In the majority of cases, if not all, the IDH mutations seen in patients with brain tumors have been heterozygous somatic mutations. Patients with Ollier disease and Maffucci syndrome, which are rare enchondromatosis syndromes, have been shown to carry mosaic mutations of IDH1 or IDH2 in non-neoplastic tissues but no patients with anaplastic astrocytoma have been shown to carry such mosaicism. Here, we present two siblings with high grade astrocytoma with IDH1 R132H mutation. Our analysis of IDH1 R132H mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells and primary teeth has identified IDH1 R132H mosaicism, using digital PCR system. IDH1 R132H mutant allelic frequencies ranging from 0.01% to 0.64% were detected in teeth, cheek cells and non-tumorous brain tissue. The findings were confirmed by next-generation sequencing with similar single nucleotide variation frequencies. Our study demonstrated an example of IDH1 R132H mosaicism in anaplastic astrocytoma patients, which could have gone unnoticed by traditional sequencing technologies.