Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

BMC Medical Genomics

Ji Won Lee¹  Hong Hoe Koo¹  Keon Hee Yoo¹  Ki Woong Sung¹  Kyunghee Park²  Eunjin Lee²  Joonho Shim³  Boram Lee³  Woong-Yang Park⁴ 

[1] Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea;Samsung Genome Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea;Samsung Genome Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea;Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea;Samsung Genome Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea;Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea;Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea;

关键词: MYCN;    Tumour mutation burden;    Mutational signature;    Genomic profile;    Immunotherapy;   

DOI  :  10.1186/s12920-020-00819-5

来源: Springer

【 摘 要 】

BackgroundMYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.MethodsFifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs.ResultsIn the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients.ConclusionsThis study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

【 授权许可】

CC BY