Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis.

The accurate assessment of disease risk remains a major goal in children with medulloblastoma. Activation of the canonical Wnt/Wingless (Wnt/Wg) signalling pathway occurs in up to 25% of cases and is associated with a favorable disease outcome. To explore the molecular pathogenesis of Wnt/Wg-active medulloblastomas, and to investigate any genetic basis for their observed clinical behavior, we assessed a series of primary medulloblastomas for evidence of Wnt/Wg pathway activation, alongside a genome-wide analysis of associated copy-number aberrations.

Combined genome-wide allelotyping and copy number analysis identify frequent genetic losses without copy number reduction in medulloblastoma.

Detailed analysis of mechanisms of genetic loss for specific tumor suppressor genes (TSGs; e.g., RB1, APC and NF1) indicates that TSG inactivation can occur by allelic loss of heterozygosity (LOH), without any alteration in DNA copy number.

Evolution and population genetics of the H-ras minisatellite and cancer predisposition.

Case-control studies have implicated rare length H-ras minisatellite alleles in cancer risk. In Europeans, this locus has four common alleles, and a larger number of rare alleles; possession of a rare allele has been identified as a risk factor responsible for 5-10% of some cancers. This unusual model of predisposition has been controversial in case-control studies, but also makes characteristic predictions about the population genetics of the locus, which we examine in this study.