Inventors:
Bert Vogelstein - Baltimore MD, US
Kenneth Kinzler - Baltimore MD, US
Nickolas Papadopoulos - Towson MD, US
Donald Williams Parsons - Bellaire TX, US
Rebecca J. Leary - Baltimore MD, US
Meng Li - San Francisco CA, US
Xiaosong Zhang - San Francisco CA, US
Sian Jones - Baltimore MD, US
Gregory J. Riggins - White Hall MD, US
Victor Velculescu - Dayton MD, US
International Classification:
C12Q 1/68
US Classification:
514 44 R, 435 611, 435 71
Abstract:
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 miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. 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 H3K4 trimethylase 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.
