The genetic and clinical significance of MYCN gain as detected by FISH in neuroblastoma.

Purpose: MYCN amplification (MYCN-A) is a strong prognostic factor in neuroblastoma (NB). MYCN gain which is a low level of MYCN-A as determined by FISH. It is unclear whether the MYCN gain is the pre-status of MYCN-A. This study assessed the status of MYCN gene and chromosome 2p of MYCN-A, MYCN gain and no MYCN amplification using a single nucleotide polymorphism (SNP) array, and the clinical implication of MYCN gain in NB.

Methods: The status of the MYCN gene was determined by FISH in 47 primary NB samples and the status of chromosome 2p in all cases was analyzed using an SNP array.

Results: 8 of the 47 cases analyzed using FISH showed MYCN-A, 7 cases showed MYCN gain and 32 cases showed no MYCN amplification. An SNP array analysis showed that only 2 of 8 cases with MYCN-A by FISH had both amplification of MYCN region and distal 2p gain and other 6 cases had amplification of the MYCN region without distal 2p gain. All 7 cases with MYCN gain by FISH had distal 2p gain without amplification of the MYCN region, and all 32 cases with no MYCN amplification by FISH demonstrated neither the amplification of the MYCN region nor the 2p gain. 5-year overall survival rate of patients with MYCN gain (n = 7, 71.4%) was not significant different from that of patients with no MYCN amplification (n = 32, 90.6%) by FISH (p = 0.11).

Conclusions: These results suggested that the MYCN gain detected by FISH represents the 2p gain, and the MYCN gain is not considered to represent the pre-status of MYCN amplification.