Methylation of PTCH1, the Patched-1 gene, in a panel of primary medulloblastomas.

The Sonic hedgehog (Shh) pathway is aberrantly activated in a subset of the most common malignant pediatric brain tumor, medulloblastoma (MB). Shh pathway activity is measured by expression of the target genes in the GLI family, MYCN and PTCH1, a tumor suppressor and negative regulator of the pathway. Promoter methylation of tumor suppressors is implicated in tumor formation by gene silencing.

A class of models for analyzing GeneChip gene expression analysis array data.

Background: Various analytical methods exist that first quantify gene expression and then analyze differentially expressed genes from Affymetrix GeneChip gene expression analysis array data. These methods differ in the choice of probe measure (quantification of probe hybridization), summarizing multiple probe intensities into a gene expression value, and analysis of differential gene expression. Research papers that describe these methods focus on performance, and how their approaches differ from others.

The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas.

To develop a genetically faithful model of medulloblastoma with increased tumor incidence compared with the current best model we activated the Sonic Hedgehog (Shh) pathway by transgenically expressing a constitutively active form of Smoothened in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This resulted in early cerebellar granule cell hyper-proliferation and a 48% incidence of medulloblastoma formation. Gene expression studies showed an increase in the known Shh targets Gli1 and Nmyc that correlated with increasing hyperplasia and tumor formation.

BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.

The mechanisms of retinoid activity in tumors remain largely unknown. Here we establish that retinoids cause extensive apoptosis of medulloblastoma cells. In a xenograft model, retinoids largely abrogated tumor growth.

Medulloblastoma growth inhibition by hedgehog pathway blockade.

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character.