ARID1B alterations identify aggressive tumors in neuroblastoma
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Soo Hyun Lee1,2,*, Jung-Sun Kim3,*, Siyuan Zheng4, Jason T. Huse2, Joon Seol Bae1, Ji Won Lee5, Keon Hee Yoo5, Hong Hoe Koo5, Sungkyu Kyung6, Woong-Yang Park1,7 and Ki W. Sung5
1Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
4Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
5Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
6Department of Bioinformatics, Sungsil University, Seoul, Republic of Korea
7Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
*These authors have contributed equally to this work
Woong-Yang Park, email: [email protected]
Ki W. Sung, email: [email protected]
Keywords: ARID1B, ALK, MYCN, neuroblastoma, sequencing
Received: July 02, 2016 Accepted: April 11, 2017 Published: April 28, 2017
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.
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