BackgroundDNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells.ResultsExamining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines.ConclusionsComparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.

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Purpose Patients with developmental dysplasia of the hip (DDH) may require a pelvic osteotomy to treat acetabular dysplasia. The Pemberton osteotomy and modified San Diego acetabuloplasty are two options available when surgically treating DDH. The purpose of this study was to compare outcomes following the Pemberton and modified San Diego when treating patients with acetabular dysplasia in typical DDH. Methods We included 45 hips in the modified San Diego group and 38 hips in the Pemberton group. Hips with less than two years follow-up and patients with a neuromuscular diagnosis were excluded. Clinical outcomes were rated using the modified McKay criteria with radiographic outcomes graded using the Severin score. Avascular necrosis (AVN) was assessed using the Kalamchi and MacEwen criteria. Results Mean follow-up was 4.9 years (2.1 to 11.2). Both procedures produced similar decreases in the acetabular index (modified San Diego: 17.0˚ versus Pemberton: 15.2˚; p = 0.846). Most hips had good/excellent results using the modified McKay criteria (modified San Diego: 78%, Pemberton: 94%; p = 0.055). Most hips were rated as good/excellent on the Severin scale (modified San Diego: 100%, Pemberton: 97%, p = 0.485). The proportion of hips with AVN grade 2 or higher were similar between groups (modified San Diego: 0%, Pemberton: 3%; p = 0.458). Conclusion The modified San Diego acetabuloplasty is a safe and effective alternative to treat acetabular dysplasia in patients with typical DDH. By maintaining an intact medial cortex, acetabular reshaping can be customized to address each patient’s specific acetabular deficiency Level of evidence Level III retrospective comparison