ARID1B alterations identify aggressive tumors in neuroblastoma

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 identifie...

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Published in:	Oncotarget Vol. 8; no. 28; pp. 45943 - 45950
Main Authors:	Lee, Soo Hyun, Kim, Jung-Sun, Zheng, Siyuan, Huse, Jason T, Bae, Joon Seol, Lee, Ji Won, Yoo, Keon Hee, Koo, Hong Hoe, Kyung, Sungkyu, Park, Woong-Yang, Sung, Ki W
Format:	Journal Article
Language:	English
Published:	United States Impact Journals LLC 11-07-2017
Subjects:	Computational Biology - methods Disease Progression DNA Copy Number Variations DNA-Binding Proteins - genetics Genetic Variation Genomics - methods Humans Mutation Neuroblastoma - drug therapy Neuroblastoma - genetics Neuroblastoma - mortality Neuroblastoma - pathology Polymorphism, Single Nucleotide Prognosis Research Paper Survival Analysis Transcription Factors - genetics ALK neuroblastoma MYCN ARID1B sequencing
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1949-2553 1949-2553
DOI:	10.18632/oncotarget.17500