MBCL-20. DETECTION OF SOMATIC MUTATIONS BY USING RNA-SEQ DATA IN CHILDHOOD MEDULLOBLASTOMA AND ITS POTENTIAL CLINICAL APPLICATION: A COHORT SERIES OF 52 CASES STUDY IN TAIWAN

Abstract

BACKGROUNDIn 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). Part of our aim was to explore the clinical application for drug target identification and finding clues to genetic predisposition.METHODSIn total, 52 frozen tumor tissues of childhood MBs were collected. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping was performed. We selected 51 clinically relevant genes for somatic variant calling using RNA-Seq data. Correlated clinical findings to genetic predisposition were defined. Potential drug targets and genetic predispositions were explored.RESULTSFour core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Potential drug targets were detected in the pathways of DNA damage response. Five patients with relevant clinical findings to genetic predisposition clustered in SHH MBs. The corresponding somatic driver mutations involved TP53, MSH6, PTEN, PTCH1, and TERT promoter (suspicious). For validation, whole exome sequencing (WES) of blood and tumor tissue was used in 10 patients with SHH MBs in the cohort series. This study included the five patients with potential genetic predispositions. Four patients exhibited relevant germline mutations named as TP53, MSH6, PTEN, and SUFU.CONCLUSIONThe findings of this study provide valuable information for personalized care of childhood MB in our cohort series and in Taiwan.