ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Application of Factorisation Methods to Analysis of Elemental Distribution Maps Acquired with a Full-Field XRF Imaging Spectrometer.

The goal of the work was to investigate the possible application of factor analysis methods for processing X-ray Fluorescence (XRF) data acquired with a full-field XRF spectrometer employing a position-sensitive and energy-dispersive Gas Electron Multiplier (GEM) detector, which provides only limited energy resolution at a level of 18% Full Width at Half Maximum (FWHM) at 5.9 keV. In this article, we present the design and performance of the full-field imaging spectrometer and the results of case studies performed using the developed instrument.

The transcriptional landscape of Shh medulloblastoma.

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN.