neuroblastomaでchromothripsis：nature

Nature
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes

Received 06 November 2011
Accepted 03 February 2012
Published online 22 February 2012

• Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour1. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)2, 3, 4, 5. Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma6. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization7, 8, 9. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours.

chromothripsisをテーマとしてこれまで報告されている論文群　(review minireviewも含む）

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