ARID1B alterations identify aggressive tumors in neuroblastoma

作者：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^*

来源：Oncotarget, 2017, 8(28): 45943-45950.

DOI：10.18632/oncotarget.17500

• ARID1B
• ALK
• MYCN
• neuroblastoma
• sequencing

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. Relapsefree 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.

• 出版日期2017-7-11