Poster Presentation Advances in Neuroblastoma Research Congress 2016

Prognostic significance of imbalanced chromosomal alterations in primary and recurrent neuroblastoma (#264)

Alexander E. Druy 1 2 3 , Egor V. Shorikov 1 2 , Grigory A. Tsaur 1 2 , Leonid I. Saveliev 1 2 3 , Larisa G. Fechina 1 2
  1. Regional Children's Hospital, Yekaterinburg, Russia
  2. Research Institute of Medical Cell Technologies, Yekaterinburg
  3. Ural State Medical University, Yekaterinburg

139 primary and 22 relapsed neuroblastoma samples were studied for copy number variations (CNVs) using MLPA. All primary and 14 relapsed tumors were obtained during core biopsy. In 8 cases of recurrence liquid biopsy of involved bone marrow has been performed. Prognostic significance was estimated by overall (OS) and event-free survival (EFS) with median of follow-up time 36 months (range 1-190 months). 

In 32 patients (23.0%) 1p deletion was revealed and had negative prognostic impact (EFS 0.38SE0.09 vs. 0.63SE0.05, p=0.010, OS 0.49SE0.09 vs. 0.71SE0.05, p=0.008). 17q gain was detected in 60 patients (43.2%), EFS 0.51SE0.07 vs. 0.63SE0.06, p=0.041, OS 0.51SE0.08 vs. 0.74SE0.06, p=0.021. Trisomy 7 discovered in 12 patients (8.6%) decreased survival: EFS 0.41SE0.16 vs. 0.59SE0.05, p=0.032; OS 0.46SE0.18 vs. 0.65SE0.05, p=0.045. Aberrations listed above retained prognostic significance in MYCN non-amplified patients.

2p23-24 gain below the MYCN amplification (MNA) level was detected in 13 patients and had negative significance in group of patients below 18 moths: both EFS and OS 0.56SE0.20 vs. 0.82SE0.06, p=0.048 and 0.92SE0.04, p=0.024.

9p deletion with haploinsufficiency of CDKN2A gene was revealed in 9 patients (6.5%) and resulted in low OS 0.38SE0.17 vs. 0.65SE0.05, p=0.032. MDM2 gene gain had negative influence on EFS in favorable groups: in infants (0.55SE0.13 vs. 0.86SE0.06, p=0.011), in patients with localized disease (0.61SE0.11 vs. 0.79SE0.06, p=0.057) and in 4S patients (0.20SE0.18 vs. 0.86SE0.13, p=0.043).

In multivariate analysis of OS stage 4 (p=0.042), MNA (p=0.049) and 9p deletion (p=0.041) demonstrated independent prognostic significance.

Investigation of CNVs in relapsed neuroblastomas revealed appearance of new alterations in 9, stable spectrum of aberrations in 3 and lack of original CNVs in 5 cases. Patients harboring new CNVs had significantly worse outcome after the recurrence comparing with those who had identical or lack of CNVs in relapse: EFS 0.00, OS 0.14SE0.13 vs. both 0.73SE0.16, p=0.014, p=0.045.