Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jun;176(6):2616-25.
doi: 10.2353/ajpath.2010.090624. Epub 2010 Apr 15.

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

Marta Jeison  1 , Shifra Ash, Gili Halevy-Berko, Jacques Mardoukh, Drorit Luria, Smadar Avigad, Galina Feinberg-Gorenshtein, Yacov Goshen, Gabriel Hertzel, Joseph Kapelushnik, Ayelet Ben Barak, Dina Attias, Ran Steinberg, Jerry Stein, Batia Stark, Isaac Yaniv
Affiliations

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

Marta Jeison et al. Am J Pathol. 2010 Jun.

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.

PubMed Disclaimer

Figures

Figure 1
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
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
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%.
See this image and copyright information in PMC

References

    1. Maris JM, Matthay KK. Molecular biology of neuroblastoma. J Clin Oncol. 1999;17:2264–2279. - PubMed
    1. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3:203–216. - PubMed
    1. London WB, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H, Thorner P, Brodeur G, Maris JM, Reynolds CP, Cohn S. Evidence for an age cut-off greater 365 days for than neuroblastoma risk group stratification in the Children’s Oncology Group. J Clin Oncol. 2005;23:6459–6465. - PubMed
    1. Brodeur GM, Pritchard J, Berthold F, Carlsen NLT, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F, Kaneko M, Kemshead J, Lampert F, Lee REJ, Look AT, Pearson ADJ, Philip T, Roald B, Sawada T, Seeger RC, Tsuchida Y, Voûte PA. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11:1466–1477. - PubMed
    1. Shimada H, Ambros I, Dehner L, Hata J, Joshi VV, Roald B, Stram DO, Gerbing RB, Lukens JN, Matthay KK, Castleberry RP. The International Neuroblastoma Pathology Classification (the Shimada System). Cancer. 1999;86:364–372. - PubMed