@article{fa4a4a1183aa4037bdf20c0c51afd1ec,
title = "Molecular-clinical correlation in pediatric medulloblastoma: A cohort series study of 52 cases in Taiwan",
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.",
keywords = "Clinical correlation, DNA damage response, Genetic predisposition, Medulloblastoma, Molecular, Risk stratification, RNA-Seq, Somatic mutations",
author = "Wu, {Kuo Sheng} and Ho, {Donald Ming Tak} and Jou, {Shiann Tarng} and Yu, {Alice L.} and Tran, {Huy Minh} and Liang, {Muh Lii} and Chen, {Hsin Hung} and Lee, {Yi Yen} and Chen, {Yi Wei} and Lin, {Shih Chieh} and Chang, {Feng Chi} and Tsai, {Min Lan} and Liu, {Yen Lin} and Lee, {Hsin Lun} and Hsieh, {Kevin Li Chun} and Huang, {Wen Chang} and Sung, {Shian Ying} and Chang, {Che Chang} and Changou, {Chun Austin} and Liang, {Kung Hao} and Hsieh, {Tsung Han} and Liu, {Yun Ru} and Chao, {Meng En} and Wan Chen and Chu, {Shing Shung} and Cho, {Er Chieh} and Wong, {Tai Tong}",
note = "Funding Information: This work was supported by Ministry of Health and Welfare grant (MOHW107-TDU-B212-114010 and MOHW 108-TDU-B212-124010 to A. L. Y. and T.T.W.); Ministry of Science and Technology grant (MOST 106-2314-B-038-032-MY2 and MOST 108-2314-B-038-061-MY3 to T.T.W.); Taipei Medical University Hospital grant (105TMU-TMUH-01-01 and 106TMU-TMUH-01-1 to T.T.W.). This manuscript was edited by Wallace Academic Editing. The authors thank Michael Taylor and the laboratory staff for helping validate the subgroup classification based on counterpart clustering of the RNA-Seq data. The authors also thank Nada Jabado and the laboratory staff for DNA methylation array and cluster analysis of our cohort series. Ching-Wen Tsai and Yen-Kuang Lin at the Biostatistics Center, Taipei Medical University helped with the survival analysis in this work. The authors thank TMU Cancer Translational Core Facility for technology support. Funding Information: Funding: This work was supported by Ministry of Health and Welfare grant (MOHW107-TDU-B212-114010 and MOHW108-TDU-B212-124010 to A. L. Y. and T.T.W.); Ministry of Science and Technology grant (MOST 106- 2314-B-038-032-MY2 and MOST108-2314-B-038-061-MY3 to T.T.W.); Taipei Medical University Hospital grant (105TMU-TMUH-01-01 and 106TMU-TMUH-01-1 to T.T.W.). Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = mar,
doi = "10.3390/cancers12030653",
language = "English",
volume = "12",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",
}