P09.01 Alterations of the RRAS and ERCC1 Genes at 19q13 in Gemistocytic Astrocytomas

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2016-10, Vol.18 (suppl_4), p.iv59-iv60
• Main Authors: Ohta, T., Yachi, K., Fukushima, T., Watanabe, T., Ohgaki, H.
• Format: Article
• Language: English
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/now188.210

Gemistocytic astrocytoma (WHO grade II) is a rare variant of diffuse astrocytoma, characterized by the presence of neoplastic gemistocytes and a significantly less favourable prognosis. Other than frequent TP53 mutations (>80%), little is known about their molecular profile. In the present study, we show that gemistocytic astrocytomas carry a lower frequency of IDH mutations than fibrillary astrocytomas (74% vs 92%; P=0.0255), but present similar profiles to fibrillary astrocytomas with respect to TERT promoter mutations (5% vs 0%), 1p/19q loss (10% vs 8%), and LOH 10q (10% vs 12%). Exome sequencing in 5 gemistocytic astrocytomas revealed homozygous deletion of genes at 19q13, i.e. RRAS (2 cases) and ERCC1 (one case). Further screening showed RRAS homozygous deletion in 7/42 (17%) gemistocytic astrocytomas and in 3/24 (13%) IDH1 mutated secondary glioblastomas. Patients with gemistocytic astrocytoma and secondary glioblastoma presenting RRAS deletion tend to have shorter survival rates than those without deletion. Differential PCR and methylation-specific PCR revealed ERCC1 homozygous deletion or promoter methylation in 10/42 (24%) gemistocytic astrocytomas and in 8/24 (33%) secondary glioblastomas. Alterations in RRAS and ERCC1 were absent in 49 fibrillary astrocytomas and 30 primary glioblastomas, suggesting that they are typical for gemistocytic astrocytomas and secondary glioblastomas.