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, Ki W. Sung

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)45943-45950
Number of pages8
JournalOncotarget
Volume8
Issue number28
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • ALK
  • ARID1B
  • MYCN
  • Neuroblastoma
  • Sequencing

ASJC Scopus subject areas

  • Oncology

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