Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Previous studies in experimental and human heart failure showed that nuclear factor kappa B (NF-κB) is chronically activated in cardiac myocytes, suggesting an important involvement of NF-κB in the cardiac remodeling process. A common insertion/deletion (-94 insertion/deletion ATTG, rs28362491) located between two putative key promoter regulatory elements in the <it>NFKB1 </it>gene was identified which seems to be the first potential functional <it>NFKB1 </it>genetic variation. The main goal of the present investigation was to investigate the <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism in relation to risk of dilated cardiomyopathy (DCM).</p> <p>Methods</p> <p>A total of 177 DCM patients and 203 control subjects were successfully investigated. The <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism was genotyped by using PCR-PAGE.</p> <p>Results</p> <p>Genotype frequency of <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism in DCM patients was significantly different from that in control subjects (<it>P </it>= 0.015) and the ATTG₂carrier (ATTG₁/ATTG₂+ ATTG₂/ATTG₂) was susceptible to DCM.</p> <p>Conclusion</p> <p>Our data suggested that <it>NFKB1 </it>-94 insertion/deletion ATTG polymorphism is associated with DCM.</p

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe