Abstract B18: MEG3 and MEG8 aberrant methylation associated with worst prognosis in an infant with neuroblastoma

Background: Neuroblastoma (NB) is an extremely rare pediatric cancer accounting for about 12% of childhood cancer-related deaths, due to its dismal prognosis in patients diagnosed over 18 months of age with disseminated disease. However, neonates and infants with neuroblastoma are expected to have a better evolution despite their stage and even unfavorable molecular characteristics. Here, we report an unusual case of low-risk neuroblastoma (stage 2B, nonamplified MYCN) in a 9-month-old girl with unfavorable outcome despite favorable prognostic factors. Material and Methods: We investigated the coding genes expression (mRNA) and long noncoding RNAs (lncRNAs) in primary and relapse tumors of this patient to look for genomic and epigenetic alterations that could explain the clinical evolution. The cytogenetic profiles of the primary and relapse tumor samples were also obtained. Three primary tumors from patients with neuroblastoma, all classified as stage 1 (INSS) and low-risk (below 18 months of age at diagnosis, nonamplified-MYCN, all alive and free of disease 60 months after diagnosis) were used as controls in RNA sequencing (RNA-Seq. Illumina®) and DNA methylation arrays (Illumina Infinium HumanMethylation450 BeadChip). Somatic copy number alterations were investigated in the primary and relapsed sample using the array-CGH methodology in a 180K platform (Agilent). Results: The cytogenetic profiles of both samples were quite identical, with few copy number alterations. No numerical chromosomal alterations (aneuploidies) were detected; both tumors carry segmental copy number alterations in common, most of them probably present in a nonmosaic state. The differential gene expression analysis based on fold-change (≤ -2 and ≥ 2), p Conclusion: Furthermore, we hypothesized that the methylation gain of the MEG3 and MEG8 locus may be accentuated during cancer progression and therefore, the increased degree of MEG3 and MEG8 suppression was associated with the overall aggressiveness of neuroblastoma. Citation Format: Estela M. Novak, Thamiris Magalhaes Gimenez, Nathalia Halley Neves, Carolina Sgarioni Camargo Vince, Ana Cristina Victorino Krepischi, Rainer Marco Lopez Lapa, Lilian M. Cristofani, Israel Bendit, Vicente Odone Filho. MEG3 and MEG8 aberrant methylation associated with worst prognosis in an infant with neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B18.