Corrigendum: Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks(Genome Res. (2016) 26:6)

The authors would like to correct the inadvertent omission of a funding source in the Acknowledgments section of the initial publication of this article. The corrected text is as follows and has been updated online. “The work performed in the laboratory of J.V. was also supported by the European Research Council (ERC AdG - GA670146 - MASCP).

Molecular analysis of iron overload in beta2-microglobulin-deficient mice.

Beta2-microglobulin knockout (beta2m-/-) mice represent an instructive model of spontaneous iron overload resembling genetic hemochromatosis. The mechanism of iron accumulation in this mouse model may be more complex than involving the MHC class I-like protein HFE. We report that beta2m-deficient mice, like Hfe-/- mice, lack the adaptive hepatic hepcidin mRNA increase to iron overload. The inverse correlation of hepatic iron levels and hepcidin mRNA expression in six beta2m-/- mice underlines the importance of hepcidin in regulating body iron stores. In contrast to Hfe-/- mice, beta2m-deficient mice display increased expression of the duodenal iron transporters DMT1 and ferroportin 1. This result implicates a broader role of beta2m in mammalian iron metabolism, suggesting that (an) additional beta2m-interacting protein(s) could be involved in controlling iron homeostasis, and highlighting the emerging connection of iron metabolism with the immune system.This study was supported by the EU QLG1-CT-1999-00665 project, the Calouste Gulbenkian Foundation/FCT Project on Hemochromatosis (Portugal) and the INNOVA Foundation/APBRF (USA)

Alternative Splicing as Driving Force in Cancer

<p>This Poster was presented in 4th DCEXS Symposium, University of Pompeu Fabra, Barcelona. This poster is about our study on alternative splicing in cancer using data generated by The Cancer Genome Atlas (TCGA) consortium. In this poster we discuss the basic data analysis pipeline and brief summary of our results. For more information here is the link to our main paper: http://biorxiv.org/content/early/2015/07/22/023010</p> <p> </p

Large-scale analysis of genome and transcriptome changes in 11 tumors uncovers novel oncogenic splicing networks

<p>Poster for:</p> <p> </p> <p>Hallmarks of Cancer: Focus on RNA</p> <p>10/09/2015 to 10/10/2015</p> <p>Amphithéâtre Constant Burg - Institut Curie</p> <p>12 rue Lhomond<br>75005 Paris<br>FRANCE</p> <p> </p

The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma

Background: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription. Conclusions: Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.status: publishe