MBRS-38. IDENTIFYING THE MOST FREQUENT VARIANTS IN PEDIATRIC MEDULLOBLASTOMA DRIVER GENES: A SINGLE INSTITUTION STUDY. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Mascaro-Cordeiro, Bruna; Oliveira, Indhira; Santos, Leonardo; Martin, Renan; Silva, Rafael; Alves, Maria Teresa; Saba-Silva, Nasjla; Dastoli, Patricia; Cavalheiro, Sergio; Toledo, Silvia
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i136
• Page End: i136
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.483
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Medulloblastoma (MB) is a malignant childhood brain tumor from cerebellum. Four principal MB molecular subgroups were established: Sonic Hedgehog (SHH), Wingless (WNT), group 3 and group 4. The present study reports the results of the first Brazilian single-institution investigation of pediatric MB subgroups-related genes. We developed an AmpliSeq TM custom panel for DNA sequencing, comprising CTNNB1, PTCH1, DDX3X, TERT and TP53 genes. We selected 28 MB treatment-naïve tumor samples. We observed two variants in exon 3 of CTNNB1, and two non-described variants in DDX3X gene. PTCH1 gene presented the highest number of variants observed (74% of samples). TP53 variants were present in 15% of samples, occurring concomitantly with PTCH1 mutations, and was related to worst overall survival (p=0.0005). Previous studies about pediatric MB genome were carried out from cohorts of North American and European populations, resulting in the identification of several genes variants. However, these variants might not be representative for other populations, mainly Brazilian population, due to the history of the current Brazilian population formation. This particularity might contribute to a very specific combination of rare and common variation, making this population interesting and enhancing the importance of the present screening study. MB occurring in pediatric patients requires deregulation of a minimal number of driver genes, and, variants that leads to deregulation of these genes may not be the same between different populations. Finally, we reinforce that new molecular diagnostic approaches involving PTCH1 and TP53 genes screening, concomitantly, can collaborate for the better clinical management of infancy and childhood MB.