Johns Hopkins University

Duke University

Donald Williams Parsons

Bert Vogelstein

Kenneth W Kinzler

Nickolas Papadopoulos

Darell D Bigner

Victor E Velculescu

Hai Yan

Meng Li

Gregory J Riggins

Sian Jones

Rebecca J Leary

Xiaosong Zhang

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.

Medulloblastoma genes as targets for diagnosis and therapeutics

Growing community of inventors

Ellicott City, MD, United States of America

Donald Williams Parsons