Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.
Cell
; 148(1-2): 59-71, 2012 Jan 20.
Article
en En
| MEDLINE
| ID: mdl-22265402
ABSTRACT
Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Reordenamiento Génico
/
Proteína p53 Supresora de Tumor
/
Meduloblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Child
/
Humans
/
Middle aged
Idioma:
En
Año:
2012
Tipo del documento:
Article