Abstract
BACKGROUND: Medulloblastoma (MB) is a highly malignant childhood brain tumor. Previous research on the genetic underpinnings of MB subtypes has predominantly focused on European and American cohorts. Given the notable genetic differences between Asian and other populations, a subtype-specific study on an Asian cohort is essential to provide comprehensive insights into MB within this demographic. The aim of this study is to investigate the genomic landscape of MB subtypes in an Asian cohort to better understand the genetic variations and potential implications for clinical practice. METHODS: We conducted a study on an Asian cohort comprising 113 MB patients. Genomic sequencing was performed using MGISEQ-2000 platform. We analyzed the participants' characteristics and compared them with previous studies. All germline variants of the ten susceptibility genes of interest (APC, BRCA2, PTCH1, PTCH2, ELP1, SUFU, CTNNB1, SMARCA4, GPR161, and TP53) were annotated and validated. RESULTS: Our study identified 14 valid germline variants that met our criteria, with these variants being detected in the genes APC, BRCA2, PTCH1, PTCH2, ELP1, and SUFU. Of these, six variants were classified as pathogenic in ClinVar: two in PTCH2 (c.C1573T), one in ELP1 (c.C583T), and three in PTCH1 (c.G1370T, c.C2066T, c.C529T). The remaining eight variants were of uncertain significance, including those in SUFU (c.T833C), ELP1 (c.T2A), BRCA2 (c.G7488C), and APC (c.C3247A, c.A1G, c.A8042G, c.A3056G, c.G822C). Our findings highlight a subtype-based germline variant landscape specific to the Asian cohort and reinforce the connection between SUFU, PTCH1, and the SHH subtype of MB. Additionally, the identification of ELP1-related cases supports the newest findings in this area and provides typical copy number variation (CNV) results for future investigation. CONCLUSIONS: This study provides valuable insights into the genetic landscape of MB in an Asian cohort, emphasizing the importance of population-specific research. The subtype-specific germline variant landscape identified in this study contributes to the understanding of MB and its genetic underpinnings in Asian populations, potentially guiding future research and therapeutic strategies.