Unveiling the mechanism of recurrence and chemoresistance in neuroblastoma using genomewide and epigenomewide analysis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: National Center for Child Health and Development (2016); Chiba Cancer Center (Research Institute) (2014-2015)
• Principal Investigator: Hishiki Tomoro 国立研究開発法人国立成育医療研究センター, 小児がんセンター, 医長 (00375776)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経芽腫 / 再発 / 網羅的ゲノム解析 / 全エクソーム解析

Outline of Final Research Achievements

The prognosis of patients with high-risk neuroblastoma is extremely poor with a 5-year survival of 40%. Approximately 70% respond to chemotherapy but half of these patients experience recurrence. Once the tumor relapses, it gains chemoresistance and the outcome of relapsed patients is dismal. We hypothesized that tumors at diagnosis and recurrent tumors have different biological features based on different genomic and epigenetic rearrangements. We thus conducted a whole exome sequence for the tumors at diagnosis and tumors at recurrence in the identical patient. In one case, we found a novel somatic mutation in the recurrent tumor in a molecule that is not involved in the Ras-MAP kinase cascade, in which molecules has previously shown to be frequently mutated in recurrent tumors. This finding suggests that a somatic mutation in a molecule distinct from the Ras-MAPK cascade could also trigger relapse and chemoresistance in neuroblastoma.

Free Research Field

小児外科学