Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome

Mutations in non-coding DNA regions are increasingly recognized as cancer drivers. These mutations can modify gene expression in cis or by inducing high-order chormatin structure modifications with long-range effects. Previous analysis reported the detection of recurrent and functional non-coding DNA mutations in the chronic lymphocytic leukemia (CLL) genome, such as those in the 3' untranslated region of NOTCH1 and in the PAX5 super-enhancer. In this report, we used whole genome sequencing data produced by the International Cancer Genome Consortium in order to analyze regions with previously reported regulatory activity. This approach enabled the identification of numerous recurrently mutated regions that were frequently positioned in the proximity of genes involved in immune and oncogenic pathways. By correlating these mutations with expression of their nearest genes, we detected significant transcriptional changes in genes such as PHF2 and S1PR2. More research is needed to clarify the function of these mutations in CLL, particularly those found in intergenic regions

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

Search for the Lepton-Flavor-Violating Decays B-s(0) -> e(+/-)mu(-/+) and B-0 -> e(+/-)mu(-/+)

A search for the lepton-flavor-violating decays B0s\u2192e\ub1\u3bc 13 and B0\u2192e\ub1\u3bc 13 is performed with a data sample, corresponding to an integrated luminosity of 1.0\u2009\u2009fb 121 of pp collisions at s 1a=7\u2009\u2009TeV, collected by the LHCb experiment. The observed number of B0s\u2192e\ub1\u3bc 13 and B0\u2192e\ub1\u3bc 13 candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be \u212c(B0s\u2192e\ub1\u3bc 13)<1.1(1.4) 710 128 and \u212c(B0\u2192e\ub1\u3bc 13)<2.8(3.7) 710 129 at 90% (95%) confidence level (C.L.). These limits are a factor of 20 lower than those set by previous experiments. Lower bounds on the Pati-Salam leptoquark masses are also calculated, MLQ(B0s\u2192e\ub1\u3bc 13)>101\u2009\u2009TeV/c2 and MLQ(B0\u2192e\ub1\u3bc 13)>126\u2009\u2009TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds