A DNA methylation map of human cancer at single base-pair resolution.

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.

Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation.

Splenic marginal zone lymphoma (SMZL) is a B-cell neoplasm whose molecular pathogenesis remains fundamentally unexplained, requiring more precise diagnostic markers. Previous molecular studies have revealed 7q loss and mutations of nuclear factor κB (NF-κB), B-cell receptor (BCR) and Notch signalling genes. We performed whole-exome sequencing in a series of SMZL cases. Results confirmed that SMZL is an entity distinct from other low-grade B-cell lymphomas, and identified mutations in multiple genes involved in marginal zone development, and others involved in NF-κB, BCR, chromatin remodelling and the cytoskeleton.

A highly specific and sensitive competitive enzyme-linked immunosorbent assay (ELISA) based on baculovirus expressed pseudorabies virus glycoprotein gE and gI complex.

A direct competition enzyme-linked immunosorbent assay (ELISA) based on baculovirus expressed complex of pseudorabies virus (PRV) glycoproteins E (gE) and I (gI) has been developed. For that purpose gE and gI genes of PRV were co-expressed in insect cells. Complex formation was confirmed by radioimmunoprecipitation assay. The specificity and sensitivity of the test were evaluated and compared with an ELISA using only gE as an antigen and a commercially available test. For validation, 245 negative sera and 165 positive sera have been tested. The gE/gI ELISA had a higher sensitivity and specificity when compared with the ELISA using only gE as the antigen. Both sensitivity and specificity were comparable with the commercially available test. Moreover, the test based on the baculovirus gE/gI complex allows the detection of anti-gE antibodies in pig serum as early as two weeks after infection. The gE/gI ELISA test is easy to perform; its additional advantage is that the gE/gI antigen can be produced in baculovirus system in large quantities without handling live pseudorabies virus.

[5-t-7-year results of cementless Endler acetabular prosthesis]. / 5- bis 7-Jahresergebnisse der zementfreien Hüftgelenkspfanne nach Endler.

From September 1980 to March 1985, 123 cementless, polyethylene Endler acetabular sockets of the threaded, tapered type were implanted in 115 patients at the department of orthopaedic surgery, Balgrist, University of Zurich. The first 102 Endler sockets, in combination with a Zweymüller femoral prosthesis, have been followed up till April 1988, this corresponding to an average observation period of 57.4 months. 12.8% of the total number of qualitative criteria and the Sutherland method, and further 20.6% of the cases were suspected of having loosened, so that a figure of 33.3% (34 loosened sockets) resulted. A definite correlation between loosening and the following factors were determined: females, limping, Trendelenburg sign, period of implantation and severe, continuous pain. No correlation was found between either tolerable pain, age, weight, or para-articular ossification, and loosening. The cementless artificial hip joint of Endler/Zweymüller combination led to a definite improvement of independency and living quality through increase in mobility and reduction of pain.