Widespread overexpression from the four DNA hypermethylated HOX clusters in aggressive (IDHwt) glioma is associated with H3K27me3 depletion and alternative promoter usage.

In human, the 39 coding HOX genes and 18 referenced noncoding antisense transcripts are arranged in four genomic clusters named HOXA, B, C, and D. This highly conserved family belongs to the homeobox class of genes that encode transcription factors required for normal development. Therefore, HOX gene deregulation might contribute to the development of many cancer types. Here, we study HOX gene deregulation in adult glioma, a common type of primary brain tumor. We performed extensive molecular analysis of tumor samples, classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found widespread expression of sense and antisense HOX transcripts only in aggressive (IDHwt) glioma samples, although the four HOX clusters displayed DNA hypermethylation. Integrative analysis of expression, DNA methylation, and histone modification signatures along the clusters revealed that HOX gene upregulation relies on canonical and alternative bivalent CpG island promoters that escape hypermethylation. H3K27me3 loss at these promoters emerges as the main cause of widespread HOX gene upregulation in IDHwt glioma cell lines and tumors. Our study provides the first comprehensive description of the epigenetic changes at HOX clusters and their contribution to the transcriptional changes observed in adult glioma. It also identified putative 'master' HOX proteins that might contribute to the tumorigenic potential of glioma stem cells.

Web-Based Tailored Nursing Intervention to Support Medication Self-management: A Qualitative Study of the Experience of Kidney Transplant Recipients.

Optimal adherence to immunosuppressive medication is essential to kidney graft success. A Web-based tailored virtual nursing intervention was developed to promote medication adherence and support self-management among kidney transplant recipients. A qualitative study was undertaken in a hospital setting in Montreal (Canada) to document how users experience the intervention and to explore medication intake self-management behaviors. To participate, transplant recipients had to be at least 18 years old and had to have completed at least one computer session of the intervention. Semistructured interviews were conducted with 10 participants (two women, eight men) with a mean age of 47.8 years. They reported receiving their latest renal transplant on average 10.6 years prior. Content analysis of the interview transcripts yielded five major themes: (1) kidney transplant is a gift from life; (2) routinization of medication intake; (3) intervention is a new and positive experience; (4) using the intervention offers many benefits; and (5) individual relevance of the intervention. Patient experience shows the intervention is acceptable and can help better manage medication intake. Results also underscore the importance of offering the intervention early in the care trajectory of transplant recipients. Web-based tailored virtual nursing interventions could constitute an easily available adjunct to existing specialized services.