Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Conceptual feasibility studies of a CO (X) -free hydrogen production from ammonia decomposition in a membrane reactor for PEM fuel cells

CO (X) -free hydrogen production from ammonia decomposition in a membrane reactor (MR) for PEM fuel cells was studied using a commercial chemical process simulator, Aspen HYSYSA (R). With process simulation models validated by previously reported kinetics and experimental data, the effect of key operating parameters such as H-2 permeance, He sweep gas flow, and operating temperature was investigated to compare the performance of an MR and a conventional packed-bed reactor (PBR). Higher ammonia conversions and H-2 yields were obtained in an MR than ones in a PBR. It was also found that He sweep gas flow was favorable for X (NH3) enhancement in an MR with a critical value (5 kmol h(-1)), above which no further effect was observed. A higher H-2 permeance led to an increased H-2 yield and H-2 yield enhancement in an MR with the reverse effect of operating temperature on the enhancement. In addition, lower operating temperature resulted in higher X (NH3) enhancement and H-2 yield enhancement as well as NG cost savings in a MR compared to a conventional PBR

Large-scale genotyping identifies 41 new loci associated with breast cancer risk

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for similar to 9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 x 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility