Abstract 1900: Prognostic significance of genetic aberrations in neuroblastoma

Abstract

Abstract Clinical behavior of neuroblastoma varies due to differences in biological characteristics of the tumor. 1p, 11q deletions, MYCN amplification (MNA) are known to be adverse prognostic markers while significance of many other copy number variations (CNV) is less clear. We analyzed 108 primary tumors with SALSA P251 and P252 MLPA neuroblastoma kits specific for loci 1p,2p,3p,11q,17q and 100 with P253 kit (4p,7q,9p,12q,14q). Prognostic significance was estimated by event-free survival (EFS) with median of follow-up time 28 months (range 1-166 months). MLPA revealed MNA in 19 patients (17.6%), in 12 cases (11.1%) NAG, DDX1 or ALK genes were coamplified with MYCN. EFS in case of MNA was significantly low comparing with normal MYCN status (0.20±0.11 vs. 0.69±0.06, p<0.001). 2p23-24 gain was observed in 15 patients (13.9%) and showed prognostic significance in patients under 1 year (EFS 0.53±0.25 vs. 0.96±0.04, p=0.047). In 29 patients (26.9%) 1p deletion was revealed. It had prognostic impact in the whole group (EFS 0.33±0.10 vs. 0.67±0.06, p=0.002) and in MYCN non-amplified patients (EFS 0.40±0.14 vs. 0.71±0.06, p=0.029). 17q gain was detected in 54 patients (50.0%) and led to decreased EFS in all patients (0.42±0.08 vs. 0.71±0.07, p<0.001) as well as in MYCN-negative subgroup (0.47±0.10 vs. 0.77±0.07, p=0.002). 4p gain detected in 8 patients (8.0%) dramatically decreased EFS in patients under 1 year of age (0.00 vs. 0.88±0.06, p=0.055). Gain of short and long arms of chromosome 7 detected in 6 patients (6.0%) led to reduced EFS in the whole group (0.33±0.19 vs. 0.56±0.06, p=0.053) and in MYCN non-amplified patients: 0.40±0.22 vs. 0.64±0.06, p=0.044. In 8 patients (8.0%) 9p deletion was found. Presence of this aberration resulted in vivid decreasing of EFS in both all evaluated patients (0.00 vs. 0.60±0.06, p=0.035) and MYCN non-amplified group (0.00 vs. 0.68±0.06, p=0.047). 3p deletion observed in 30 of 108 patients (27.8%) had adverse prognostic significance in the group of patients above 3 years of age (EFS 0.25±0.23 vs. 0.71±0.11, p=0.034). Neither interstitial (n=16, 14.8%) nor terminal (n=9, 8.3%) 11q deletions had prognostic significance in our series: EFS 0.28±0.14 and 0.78±0.14 vs. 0.60±0.06, p=0.164 and p=0.477 respectively. No influence on EFS was found in case of presence 12q or MDM2 gene gain (n= 20, 20.0%) and 14q aberrations (n=14, 14.0%). Thus, MLPA is accurate technique for CNV detection in neuroblastoma. In our cohort of patients, treated according GPOH NB2004 protocol, MNA, 1p, 9p deletions and 17q gain demonstrated negative influence on EFS. Presence of 2p23-24 gain and 4p gain led to decrease EFS in the group of patients below 1 year old, while 1p and 9p deletions, 17q gain and gain of both arms of chromosome 7 retained prognostic significance in MYCN non-amplified patients. Coamplification of MYCN gene with DDX1, NAG and ALK genes had no prognostic significance comparing with amplification of MYCN gene alone. Citation Format: Alexander E. Druy, Grigory A. Tsaur, Egor V. Shorikov, Alexander M. Popov, Leonid I. Saveliev, Larisa G. Fechina. Prognostic significance of genetic aberrations in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1900. doi:10.1158/1538-7445.AM2014-1900