JCO: The incidence of ALK genetic variants in high-risk neuroblastoma and its impact on prognosis

In neuroblastoma (NB), ALK receptor tyrosine kinase can be constitutively activated by activating point mutations or gene amplification
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The HR-NBL1/SIOPEN trial studied ALK gene mutations in high-risk (HR) NB patients to determine its frequency, correlation with clinical parameters, and impact on prognosis

A total of 1092 HR-NBL1/SIOPEN patients’ diagnostic tumor samples were collected, and the ALK amplification status (n=330), ALK mutation profile (n=191) or both (n=571) were analyzed.

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diagnosis

Location and frequency of point mutations in ALK

Location and frequency of point mutations in ALK

Genome ALK amplification (ALKa) was detected in 4.
5% of cases (41/901) , except for one case with MYCN amplification (MNA)
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ALKa is associated with significantly poorer overall survival (OS) (5-year OS: ALKa[n=41] vs no ALKa[n=860]: 28%[95% CI 15-42] vs 51%[47-54 ]; P<.

Genome ALK amplification (ALKa) was detected in 4.

Prognosis of patients with different genetic variants of ALK

Prognosis of patients with different genetic variants of ALK

Among the 571 cases with known ALKa and ALKm status, there were significant differences in OS between cases with ALKa or clonal ALKm and cases with subclonal ALKm or without ALK mutations (5-year OS was 26% or 33%, respectively) 48% or 51%; P=0.
001)
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Importantly, in the multivariate model, more than one metastatic compartment is involved (hazard ratio [HR] 2.

Among the 571 cases with known ALKa and ALKm status, there were significant differences in OS between cases carrying ALKa or clonal ALKm and cases carrying subclonal ALKm or without ALK mutation.

For patients with high-risk neuroblastoma, ALK genetic variation (clonal mutation or amplification) is an independent predictor of poor survival prognosis.

Original source:

Bellini Angela,P?tschger Ulrike,Bernard Virginie et al.

Frequency and Prognostic Impact of Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1) in this message