P20.08.b clinical and molecular analyses of a series of adult pilocytic astrocytoma

Abstract BACKGROUND Pilocytic astrocytoma (PA) is a rare, grade 1 subtype of glioma. It is most frequent during the first two decades of life, the incidence rate decreasing with age. PAs are usually located in the cerebellum, although they have also been described in other sites. They are circumscribed, solid-cystic, with low cellularity and generally slow-growing tumours with good prognosis in the paediatric age group. PA is associated with MAPK pathway dysregulation, most often showing BRAF gene alterations. PA is very rare in older adults and is associated in some cases with a worse prognosis. In this work we set out to analyse a series of adult PA from a clinical, morphological and molecular point of view. MATERIAL AND METHODS Clinical data were collected from a group of adult patients diagnosed with PA. Nucleic acid extraction was performed by automated extraction and the samples were analysed through a 30-gene targeted panel for gliomas by using Next-Generation Sequencing. Tandem duplication causing fusion of KIAA1549 and BRAF genes (K-B fusion) was analysed by RT-PCR. RESULTS Thirty-four patients were included, with a mean age of 34.4 years (range, 18-57 years). The male/female ratio was 26/8. Mean overall survival was 150.5 months, with more than 10 years of mean follow-up. At the time of the last review, 91% (30/33) of the patients remained alive, while the remaining 9% (3/33) died. Neuroanatomic locations (31 cases) were as follows: cerebrum/lobar 23% (7), cerebellum 39% (12), brainstem 10% (3), ventricle 6% (2), spinal cord 10% (3), optic nerve 13% (4). The K-B fusion was detected in 44% of cases (8/18). Of these, 87.5% (7/8) and 12.5% (1/8) showed fusions involving exons 16:9 and 15:9, respectively. K-B positive cases had a mean age of 40 years. Analyses by NGS revealed mutations in NF1 (15%), BRAF (11%), PDGFRA (11%), EGFR (7%) and PIK3CA (7%). Other variants observed in 4% of cases involved ATRX, CIC, IDH1, KEL, KRAS, MET, MSH6, PTPN11 and RB1. No alterations were detected in 3 of the cases, suggesting that other untested driver alterations could be present. CONCLUSION In this series, no significant differences with childhood PA in the frequency of molecular alterations were observed, in contrast to other gliomas where there are strong differences in the molecular alterations between adult and paediatric tumours. The most common genetic alterations in adult PA involved the MAPK pathway, as previously reported. In contrast to other adult PA studies, the frequency of K-B fusion was similar to that of paediatric PA. Molecular alterations related to an aggressive behaviour or to other glioma types were identified, such as mutations of ATRX, PDGFRA, NF1 or PI3KCA, which can suggest other tumour types. Our results suggest the need for multilayer histological and molecular diagnosis to appropriately manage adult PA.