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.

[The long-term efficacy of fibrinolytic treatment in the acute phase of a myocardial infarct. A comparison with a control group]. / Eficacia a largo plazo del tratamiento fibrinolítico en la fase aguda del infarto de miocardio. Comparación con un grupo control.

BACKGROUND: The follow-up of patients with an acute myocardial infarction treated with fibrinolysis and that of patients treated with conventional therapy was analyzed. PATIENTS AND METHODS: The study cohort included: 1) 214 patients with a first acute infarction of < or = 4 hours and with < or = 70 years of age who participated in a randomized study comparing the effects of streptokinase (SK, n: 110) vs conventional treatment (control, n: 104), and 2) a total of 361 patients with a myocardial infarction of < or = 6 hours and < or = 75 years old treated with fibrinolytic agents. RESULTS: In-hospital mortality in the randomized study was 11% for the control group and 7% for the SK group, and 8.8% for the rest of patients treated with fibrinolysis. Mortality during follow-up in the randomized study (7.0 +/- 1.5 years) was 10.7% for the SK group and 19.3% for the control group. Ejection fraction was significantly lower in non survivors than in survivors (36.7% vs 50.8%, (p < 0.0001) and among patients with an ejection fraction < 50%, follow-up mortality was significantly lower in those with a complete recanalization (TIMI 3) than in those with an absent or incomplete recanalization (TIMI 0-2) (98% vs 22%). Follow-up mortality for the rest of patients treated with fibrinolysis (2.6 +/- 1.6 years) was 9%. CONCLUSIONS: 1) The reduction of in-hospital mortality by fibrinolysis appears to increase in the long-term follow-up, and 2) the long-term survival seems to be related not only to the left ventricular function but also to the extent of angiographic recanalization.