Project description:Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. The training set consisted of 96 samples for which relapse status at 30 months post-treatment was known. Matched normal blood samples were collected through the COG Tumor Bank (protocol ACNS02B3) and from Children's Hospital Boston under institutional review board approval. The test set included 78 samples: 47 samples from our original study6 not used for training, 16 samples from Kool et al,33 and 15 samples from the COG Tumor Bank. All training and test samples correspond to patients at least 3 years old treated with conventional chemotherapy, surgical resection, and craniospinal irradiation. In the test set, 15 samples (Children's Oncology Group Tumor Bank) were processed as described above. Of those 15, a total of six have DNA copy number data. Another set of 47 samples was taken from the data set from Pomeroy et al. (Affymetrix Hu6800; Affymetrix). None of those samples had DNA copy number data. The remaining 16 samples, all with DNA copy number data, came from Kool et al. (Affymetrix U133; Affymetrix).
Project description:Bank voles are susceptible to prion strains from many different species, yet the molecular mechanisms underlying the ability of bank vole prion protein (BVPrP) to function as a universal prion acceptor remain unclear. Potential differences in molecular environments and protein interaction networks on the cell surface of brain cells may contribute to BVPrP’s unusual behavior. To test this hypothesis, we generated knock-in mice that express physiological levels of BVPrP (M109 isoform) and employed mass spectrometry to compare the interactomes of mouse (Mo) PrP and BVPrP following mild in vivo crosslinking of brain tissue. Substantial overlap was observed between the top interactors for BVPrP and MoPrP, with established PrP-interactors such as neural cell adhesion molecules, subunits of Na+/K+-ATPases, and contactin-1 being equally present in the two interactomes. We conclude that the molecular environments of BVPrP and MoPrP in the brains of mice are very similar. This suggests that the unorthodox properties of BVPrP are unlikely to be mediated by differential interactions with other proteins.
Project description:MicroRNA expression pattern in 20 pairs of primary lung cancers and their corresponding non cancerous lung tissues. These specimens were obtained from the Nice Hospital Tumor Bio Bank, France.