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Mutational signatures of ionizing radiation in second malignancies.
(NATURE PUBLISHING GROUP, 2016-09-12)
Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched ...
Pan-cancer analysis of the extent and consequences of intratumor heterogeneity.
(NATURE PUBLISHING GROUP, 2016-01-01)
Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect ...
Should tissue structure suppress or amplify selection to minimize cancer risk?
(2016-08-01)
Background: It has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, ...
DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes
(2016-01-01)
Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and ...
Integrated multiomics approach identifies calcium and integrin-binding protein-2 as a novel gene for pulse wave velocity
(Ovid Technologies (Wolters Kluwer Health), 2016-01-01)
Background: Carotid-femoral pulse wave velocity (PWV) is an important measure of arterial stiffness, which is an independent predictor of cardiovascular morbidity and mortality. In this study, we used an integrated genetic, ...
Novel regional age-associated DNA methylation changes within human common disease-associated loci
(2016-01-01)
Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional ...
Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53-dependent mechanism
(Springer Science and Business Media LLC, 2016-02-01)
The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation ...
Subcellular protein expression models for microsatellite instability in colorectal adenocarcinoma tissue images
(2016-10-01)
Background: New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. ...
2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19.
(AMER CHEMICAL SOC, 2016-06-09)
We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid ...
Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.
(ROCKEFELLER UNIV PRESS, 2016-05-30)
Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In ...