AI Article Synopsis
- Targeted panel sequencing of 72 children with neuroblastoma revealed significant genetic alterations in genes like ALK (16.7%) and BRCA1 (13.9%), with 22.2% of patients identified as having potential molecular targets for therapy.
- Two-thirds of the ALK mutations were linked to increased efficacy of ALK inhibitors, while ARID1B mutations were found in 6.9% of patients, mostly in high-risk cases, with a concerning association to disease progression.
- Patients with ARID1B alterations or MYCN amplification showed significantly lower survival rates compared to those without these genetic changes, highlighting the need for targeted therapies and the identification of poor prognostic subgroups in neuroblastoma.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542239 | PMC |
| http://dx.doi.org/10.18632/oncotarget.17500 | DOI Listing |
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