|Title:||Molecular-clinical correlation in pediatric medulloblastoma: A cohort series study of 52 cases in Taiwan||Authors:||Wu K.-S.
|Keywords:||Clinical correlation; DNA damage response; Genetic predisposition; Medulloblastoma; Molecular; Risk stratification; RNA-Seq; Somatic mutations||Issue Date:||2020||Publisher:||MDPI AG||Journal Volume:||12||Journal Issue:||3||Start page/Pages:||653||Source:||Cancers||Abstract:||
In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
|ISSN:||2072-6694||DOI:||10.3390/cancers12030653||SDG/Keyword:||adolescent; Article; cancer radiotherapy; cancer surgery; child; childhood cancer; cohort analysis; correlational study; DNA damage response; DNA methylation; female; genetic predisposition; genetic variation; germline mutation; human; major clinical study; male; medulloblastoma; molecular genetics; personalized medicine; preschool child; RNA sequencing; somatic mutation; Taiwan; whole exome sequencing
|Appears in Collections:||醫學系|
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