Abstract 77: Genomic characterization of aggressive subtype of neuroblastoma without MYCN amplification

Abstract

Abstract Neuroblastoma is known to exhibit wide ranges of clinical behavior, from spontaneous regression to highly resistant to chemotherapy, and one of the challenges in the clinic is to develop adequate therapeutic strategies for the intermediate risk-type of patients (stage 3 or 4 without MYCN amplification) whose prognosis sometimes tends to be poor in long-time follow-up (10 years survival rate (SR) was 51% in our database, n = 161). To discover the key target genes or pathways for the unfavorable subset in this patient group, we have analyzed 44 primary tumors (dead:24, alive:20) without MYCN amplification nor ALK alteration by integrated genomic analyses such as array CGH, gene expression profiling and whole exome sequencing (SureSelect 50Mb, average read depth:157, x20 coverage:95%). We found 816 non-synonymous somatic single nucleotide variations (SNVs) in coding genes and alteration number in each tumor strongly associates with age at diagnosis (p<0.0001) and patient prognosis (p = 0.187). A novel ATRX mutation was identified in a tumor with 1p and 11q losses isolated from a male patient (age:93 months). Recurrent SNVs (n = 2 to n = 6) were found in 44 genes, 20 of those were involved only in the tumors from the patient with poor prognosis, in the 44 tumor set. Validation of these 20 SNVs is ongoing by using additional clinical samples. These features of genomic alterations could be useful for risk classification for each tumor and constructing new therapeutic strategies for aggressive neuroblastomas without MYCN amplification. Citation Format: Miki Ohira, Kenji Tatsuno, Shuichi Tsutsumi, Shogo Yamamoto, Yohko Nakamura, Takehiko Kamijo, Hiroyuki Aburatani, Akira Nakagawara. Genomic characterization of aggressive subtype of neuroblastoma without MYCN amplification. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 77. doi:10.1158/1538-7445.AM2015-77