ARID1B alterations identify aggressive tumors in neuroblastoma
| Autor: | Ki Woong Sung, Woong-Yang Park, Soo Hyun Lee, Jung-Sun Kim, Keon Hee Yoo, Ji Won Lee, Siyuan Zheng, Joon Seol Bae, Jason T. Huse, Hong Hoe Koo, Sungkyu Kyung |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Gerontology medicine.medical_specialty Poor prognosis DNA Copy Number Variations medicine.medical_treatment Polymorphism Single Nucleotide Targeted therapy 03 medical and health sciences Neuroblastoma Internal medicine MYCN medicine Humans In patient Survival analysis Molecular cell biology Molecular pathology business.industry Disease progression Computational Biology Genetic Variation sequencing Genomics medicine.disease Prognosis Survival Analysis ARID1B DNA-Binding Proteins 030104 developmental biology ALK Mutation Disease Progression business Research Paper Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Soo Hyun Lee 1, 2, * , Jung-Sun Kim 3, * , Siyuan Zheng 4 , Jason T. Huse 2 , Joon Seol Bae 1 , Ji Won Lee 5 , Keon Hee Yoo 5 , Hong Hoe Koo 5 , Sungkyu Kyung 6 , Woong-Yang Park 1, 7 and Ki W. Sung 5 1 Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea 2 Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 4 Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA 5 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 6 Department of Bioinformatics, Sungsil University, Seoul, Republic of Korea 7 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Woong-Yang Park, email: woongyang.park@samsung.com Ki W. Sung, email: kwsped@skku.edu Keywords: ARID1B, ALK, MYCN, neuroblastoma, sequencing Received: July 02, 2016 Accepted: April 11, 2017 Published: April 28, 2017 ABSTRACT Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without ( p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis. |
| Databáze: | OpenAIRE |
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