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Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139704/ https://www.ncbi.nlm.nih.gov/pubmed/32168907 http://dx.doi.org/10.3390/cancers12030653 |
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author | Wu, Kuo-Sheng Ho, Donald Ming-Tak Jou, Shiann-Tarng Yu, Alice L. Tran, Huy Minh Liang, Muh-Lii Chen, Hsin-Hung Lee, Yi-Yen Chen, Yi-Wei Lin, Shih-Chieh Chang, Feng-Chi Tsai, Min-Lan Liu, Yen-Lin Lee, Hsin-Lun Hsieh, Kevin Li-Chun Huang, Wen-Chang Sung, Shian-Ying Chang, Che-Chang Changou, Chun Austin Liang, Kung-Hao Hsieh, Tsung-Han Liu, Yun-Ru Chao, Meng-En Chen, Wan Chu, Shing-Shung Cho, Er-Chieh Wong, Tai-Tong |
author_facet | Wu, Kuo-Sheng Ho, Donald Ming-Tak Jou, Shiann-Tarng Yu, Alice L. Tran, Huy Minh Liang, Muh-Lii Chen, Hsin-Hung Lee, Yi-Yen Chen, Yi-Wei Lin, Shih-Chieh Chang, Feng-Chi Tsai, Min-Lan Liu, Yen-Lin Lee, Hsin-Lun Hsieh, Kevin Li-Chun Huang, Wen-Chang Sung, Shian-Ying Chang, Che-Chang Changou, Chun Austin Liang, Kung-Hao Hsieh, Tsung-Han Liu, Yun-Ru Chao, Meng-En Chen, Wan Chu, Shing-Shung Cho, Er-Chieh Wong, Tai-Tong |
author_sort | Wu, Kuo-Sheng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7139704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71397042020-04-10 Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan Wu, Kuo-Sheng Ho, Donald Ming-Tak Jou, Shiann-Tarng Yu, Alice L. Tran, Huy Minh Liang, Muh-Lii Chen, Hsin-Hung Lee, Yi-Yen Chen, Yi-Wei Lin, Shih-Chieh Chang, Feng-Chi Tsai, Min-Lan Liu, Yen-Lin Lee, Hsin-Lun Hsieh, Kevin Li-Chun Huang, Wen-Chang Sung, Shian-Ying Chang, Che-Chang Changou, Chun Austin Liang, Kung-Hao Hsieh, Tsung-Han Liu, Yun-Ru Chao, Meng-En Chen, Wan Chu, Shing-Shung Cho, Er-Chieh Wong, Tai-Tong Cancers (Basel) Article 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. MDPI 2020-03-11 /pmc/articles/PMC7139704/ /pubmed/32168907 http://dx.doi.org/10.3390/cancers12030653 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Kuo-Sheng Ho, Donald Ming-Tak Jou, Shiann-Tarng Yu, Alice L. Tran, Huy Minh Liang, Muh-Lii Chen, Hsin-Hung Lee, Yi-Yen Chen, Yi-Wei Lin, Shih-Chieh Chang, Feng-Chi Tsai, Min-Lan Liu, Yen-Lin Lee, Hsin-Lun Hsieh, Kevin Li-Chun Huang, Wen-Chang Sung, Shian-Ying Chang, Che-Chang Changou, Chun Austin Liang, Kung-Hao Hsieh, Tsung-Han Liu, Yun-Ru Chao, Meng-En Chen, Wan Chu, Shing-Shung Cho, Er-Chieh Wong, Tai-Tong Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title | Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title_full | Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title_fullStr | Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title_full_unstemmed | Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title_short | Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan |
title_sort | molecular-clinical correlation in pediatric medulloblastoma: a cohort series study of 52 cases in taiwan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139704/ https://www.ncbi.nlm.nih.gov/pubmed/32168907 http://dx.doi.org/10.3390/cancers12030653 |
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