2p24 Gain region harboring MYCN gene compared with MYCN amplified and nonamplified neuroblastoma: biological and clinical characteristics

Abstract

Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear. The aim of this study was to compare the biological and clinical characteristics of these tumors with MYCN amplified and nonamplified neuroblastoma and to determine their impact on disease outcome. Samples from 177 patients were analyzed by fluorescence in situ hybridization, including MYCN, 1p, 17q, and 11q regions; 2p gain was identified in 25 patients, MYCN amplification in 31, and no amplification in 121 patients. Patients with 2p gain had a significantly worse 5-year event-free survival rate than patients with no MYCN amplified (P < 0.001), and an intermediate 5-year overall survival rate difference existed between the MYCN amplified tumors (P = 0.025) and nonamplified (P = 0.003) groups. All of the 2p gain samples were associated with segmental and/or numerical alterations in the other tested regions. The presence of segmental alterations with or without MYCN amplification was recently found to be the strongest predictor of relapse in a multivariate analysis. The results of the present study suggest that the determination of MYCN gene copy number relative to chromosome 2, when evaluating MYCN status at diagnosis, may help to reveal the underlying genetic pattern of these tumors and better understand their clinical behavior.

Figure 1

A: MLPA corresponding to pt. 171 showing 2p region gain (red square), accompanied by other segmental imbalances: chromosomes 1p⁻, 3p⁻, 11q⁻, +12p, and +17q. B: FISH showing same copy number of MYCN and ALK gene (pt. 2).

Figure 2

EFS and OS for the whole cohort according to MYCN status. A: 5-year EFS MYCN balanced: balanced number of MYCN and cep2/LAF genes: 78% ± 4%; 2p/MYCN gain: 40% ± 13%; and MYCN amplified: 29% ± 8%. B: 5-year OS MYCN balanced: 85% ± 4%; 2p gain: 51% ± 14%; and MYCN amplified: 34% ± 10%.

Figure 3

EFS and OS of 2p/MYCN gain group according to 11q status. A: 5-year EFS 11q normal: 34% ± 2%; 11q loss: 33% ± 17%. B: 5-year OS 11q normal: 38% ± 29%; 11 q loss: 46% ± 16%.