The genetic landscape of the childhood cancer medulloblastoma

By D. W. Parsons, M. Li, Xiaosong Zhang, Siân Jones, R. Leary, Jimmy Lin, S. Boca, Hannah Carter, Josue Samayoa, C. Bettegowda and 37 more. Science, 2010

734 citations recorded by the source corpus.

Genomic analysis of a childhood cancer reveals markedly fewer mutations than what is typically seen in adult cancers. Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

Subfields: Genetics, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/82674fa8320a147710dae0101441bcc41113076a

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Citations in the corpus

Cancer heterogeneity—a multifaceted view (2013, positive): “Individual cancers can harbour from a handful [15,16] to hundreds of mutations [17].”
Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations (2012, positive): “One of these genes, NEB, was recently reported to harbor somatic point mutations in medulloblastoma (Parsons et al., 2011), suggesting that the resulting fusion gene may play a crucial role in the respective tumor.”
Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder (2011, methodology): “However, our data, as well as the mutation data recently deposited in COSMIC database (see URLs ), supported that MLL and its homolog MLL3 are likely to act recessively in some solid tumor”
SWI/SNF nucleosome remodellers and cancer (2011, background): “ARID1A is also occasionally mutated in medulloblastomas, the most common malignant brain tumour of childre”
The whole-genome landscape of medulloblastoma subtypes (2017, positive): “Consistent with our previous studies 23,24 , genetic events targeting histone modifiers, especially those regulating lysine methylation and/ or acetylation, were found across subgroups and contributed to a considerable proportion of cases (Extended Data Fig.”