Oncotarget

Research Papers:

ARID1B alterations identify aggressive tumors in neuroblastoma

Soo Hyun Lee, Jung-Sun Kim, Siyuan Zheng, Jason T. Huse, Joon Seol Bae, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Sungkyu Kyung, Woong-Yang Park _ and Ki Woong Sung

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Oncotarget. 2017; 8:45943-45950. https://doi.org/10.18632/oncotarget.17500

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Abstract

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

Correspondence to:

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

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.


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