1671P PRECISEKIDS: A nation-wide project for the comprehensive genomic profiling of paediatric solid tumours in Portugal

Abstract

Paediatric solid tumours (PST) are a leading cause of death in children aged 1-19 years. Our aim was to create a national network for the efficient delivery of a comprehensive genomic profiling of PST. A protocol between a molecular diagnostics laboratory and 3 reference centres in paediatric oncology was implemented. The protocol is active since January 2021 with the following inclusion criteria: age 0-18; newly diagnosed solid tumour/tumour like lesions; previously diagnosed solid tumour/tumour like lesion, presenting as refractory/relapsed disease; availability of tumour material; informed consent. Tumours were reviewed by expert pathologists and profiled with Oncomine Childhood Cancer Research Assay. As of April 2022, we have molecularly profiled 97 PST, of which 39 were brain tumours (PBT) and 58 were extra-cranial solid tumours (PECST). Among PBT, BRAF was the most frequently altered gene, while other commonly mutated genes were PIK3CA and FGFR, the former in high grade gliomas (HGG) and the latter in low grade gliomas (LGG). HGG showed a more complex profile, with many cases harbouring multiple alterations in EGFR, H3F3A, HIST1H3B, TP53, among others. Ependymomas and medulloblastomas were the tumour types with fewer molecular alterations. Within PECST, we were able to detect the pathognomonic molecular alterations in several tumours. Some of the molecular findings were important for differential diagnosis, such as FGFR and BRAF alterations in LGG, a H3F3A mutation in a giant cell tumour of the bone and a novel STAG2-MAMLD1 fusion in a bone lesion. Additional molecular alterations might prove valuable for targeted therapy, namely BRAF and PIK3CA in LGG and vascular malformations, MAP2K1 in systemic Langerhans cell histiocytosis and a TFG-ROS1 fusion in a myofibroblastic inflammatory tumour. Overall, we detected biologically relevant molecular alterations in 42/58 (72%) of PECST and in 28/39 (72%) of PBT, most of which with clinical relevance, at the level of diagnosis, prognosis or therapy selection. A subset of the patients is already undergoing targeted therapy, mainly using BRAF or MEK inhibitors with good clinical response in general.