Copy number gain of MYCN gene is a recurrent genetic aberration and favorable prognostic factor in Chinese pediatric neuroblastoma patients

Miao Wang,Chunju Zhou,Rongqin Cai,Liping Gong,Yong Li

doi:10.1186/1746-1596-8-5

Miao Wang, Chunju Zhou + Show 3 more

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https://doi.org/10.1186/1746-1596-8-5

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Abstract

BackgroundAmplification of MYCN oncogene is an established marker indicating aggressive tumor progression of neuroblastoma (NBL). But copy number analyses of MYCN gene in ganglioneuroblastoma (GNBL) and ganglioneuroma(GN) is poorly described in the literature. In the study, we evaluated the copy number aberrations of MYCN gene in clinical samples of NBLs, GNBLs and GNs and analyzed their association with clinical outcome of the patients.MethodsIn this study, we analyzed MYCN gene and chromosome 2 aneusomy by using fluorescence in situ hybridization (FISH) method in a total of 220 patients with NBL, GNBL and GN cases. Kaplan-Meier curves were generated by using SPSS 12.0 software.ResultsOf 220 patients, 178 (81.0%) were NBLs, 32 (14.5%) were GNBLs and 10 (4.5%) were GNs. MYCN gain is a recurrent genetic aberration of neuroblastic tumors (71.8%, 158/220), which was found in 129 NBLs (58.6%, 129/220), 25 GNBLs (11.4%, 25/220) and 4 GN cases (1.8%, 4/220). However, MYCN amplification was only present in 24 NBL tumors (13.5%, 24/178) and 1 GNBL case (3.1%, 1/32). Kaplan-Meier survival analysis indicated that MYCN amplification is significantly correlated with decreased overall survival in NBLs (P=0.017). Furthermore, a better prognosis trend was observed in patients with MYCN gain tumors compared with those with MYCN gene normal copy number tumors and MYCN amplification tumors (P=0.012).ConclusionsIn summary, the frequency of MYCN amplification in NBLs is high and is rarely observed in GNBLs and GNs, which suggest MYCN plays an important role in neuroblastic tumors differentiation. MYCN gain appeared to define a subgroup of NBLs with much better outcome and classification of MYCN gene copy number alteration as three groups (amplification, gain and normal) can provide a powerful prognostic indicator in NBLs.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6417541528559124

Highlights

Amplification of MYCN oncogene is an established marker indicating aggressive tumor progression of neuroblastoma (NBL)
Clinical features We analyzed a panel of 220 pediatric patient samples comprising 178 NBLs, 32 GNBLs, and 10 GNs
Patients with NBL were significantly younger than patients with GN and GNBL (P < 0.001)

Summary

Introduction

Amplification of MYCN oncogene is an established marker indicating aggressive tumor progression of neuroblastoma (NBL). Copy number analyses of MYCN gene in ganglioneuroblastoma (GNBL) and ganglioneuroma(GN) is poorly described in the literature. We evaluated the copy number aberrations of MYCN gene in clinical samples of NBLs, GNBLs and GNs and analyzed their association with clinical outcome of the patients. Peripheral neuroblastic tumors (NTs) including neuroblastoma(NBL), ganglioneuroblastoma(GNBL), and ganglioneuroma(GN) comprise one of the most common groups of neoplastic disease in infants and children. Amplification of MYCN oncogene is an established marker indicating aggressive tumor progression of NBL [2,3]. Copy number status of MYCN gene in GNBL and GN is poorly described in the literature [13]

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