Biochemical and molecular epidemiology of human cancer: indicators of carcinogen exposure, DNA damage, and genetic predisposition.

Structural controllability is the generalization of traditional controllability for dynamical systems. During the last decade, interesting biological discoveries have been inferred by applied structural controllability analysis to biological networks. However, false positive/negative information (i.e. nodes and edges) widely exists in biological networks that documented in public data sources, which can hinder accurate analysis of structural controllability. In this study, we propose WDNfinder, a comprehensive analysis package that provides structural controllability with consideration of node connection strength in biological networks. When applied to the human cancer signaling network and p53-mediate DNA damage response network, WDNfinder shows high accuracy on essential nodes prediction in these networks. Compared to existing methods, WDNfinder can significantly narrow down the set of minimum driver node set (MDS) under the restriction of domain knowledge. When using p53-mediate DNA damage response network as illustration, we find more meaningful MDSs by WDNfinder. The source code is implemented in python and publicly available together with relevant data on GitHub: https://github.com/dustincys/WDNfinder .

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DNA Damage Checkpoint Signaling Pathways in Human Cancer

Signaling Pathways in Cancer Pathogenesis and Therapy ◽

10.1007/978-1-4614-1216-8_3 ◽

2011 ◽

pp. 23-37

Author(s):

Robert T. Abraham ◽

Thanos D. Halazonetis

Keyword(s):

Dna Damage ◽

Signaling Pathways ◽

Human Cancer ◽

Dna Damage Checkpoint ◽

Checkpoint Signaling

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Colibactin DNA damage signature indicates causative role in colorectal cancer

10.1101/819854 ◽

2019 ◽

Cited By ~ 4

Author(s):

Paulina J. Dziubańska-Kusibab ◽

Hilmar Berger ◽

Federica Battistini ◽

Britta A. M. Bouwman ◽

Amina Iftekhar ◽

...

Keyword(s):

Dna Damage ◽

Human Cancer ◽

Colorectal Cancers ◽

Causative Role ◽

Sequence Motifs ◽

Dna Double Strand Breaks ◽

Colon Cells ◽

Binding Characteristics ◽

Significant Enrichment ◽

Dynamics Simulations

AbstractColibactin, a potent genotoxin of Escherichia coli, causes DNA double strand breaks (DSBs) in human cells. We investigated if colibactin creates a particular DNA damage signature in infected cells by identifying DSBs in colon cells after infection with pks+ E.coli. Interestingly, genomic contexts of DSBs were enriched for AT-rich penta-/hexameric sequence motifs, exhibiting a particularly narrow minor groove width and extremely negative electrostatic potential. This corresponded with the binding characteristics of colibactin to double-stranded DNA, as elucidated by docking and molecular dynamics simulations. A survey of somatic mutations at the colibactin target sites of several thousand cancer genomes revealed significant enrichment of the identified motifs in colorectal cancers. Our work provides direct evidence for a role of colibactin in the etiology of human cancer.One sentence summaryWe identify a mutational signature of colibactin, which is significantly enriched in human colorectal cancers.

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Somatic mutations in human cancer: applications in molecular epidemiology

Revue d Épidémiologie et de Santé Publique ◽

10.1016/s0398-7620(05)84603-6 ◽

2005 ◽

Vol 53 (3) ◽

pp. 257-266 ◽

Cited By ~ 7

Author(s):

E. Le Roux ◽

E. Gormally ◽

P. Hainaut

Keyword(s):

Molecular Epidemiology ◽

Somatic Mutations ◽

Human Cancer

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Experimental Models to Define the Genetic Predisposition to Liver Cancer

Cancers ◽

10.3390/cancers11101450 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1450 ◽

Cited By ~ 1

Author(s):

Rosa M. Pascale ◽

Maria M. Simile ◽

Graziella Peitta ◽

Maria A. Seddaiu ◽

Francesco Feo ◽

...

Keyword(s):

Genetic Predisposition ◽

Molecular Mechanisms ◽

Human Cancer ◽

Gene Transfection ◽

Experimental Models ◽

Environment Interaction ◽

Rat Strains ◽

Susceptible Mouse ◽

Resistant Mouse ◽

Neoplastic Lesions

Hepatocellular carcinoma (HCC) is a frequent human cancer and the most frequent liver tumor. The study of genetic mechanisms of the inherited predisposition to HCC, implicating gene–gene and gene–environment interaction, led to the discovery of multiple gene loci regulating the growth and multiplicity of liver preneoplastic and neoplastic lesions, thus uncovering the action of multiple genes and epistatic interactions in the regulation of the individual susceptibility to HCC. The comparative evaluation of the molecular pathways involved in HCC development in mouse and rat strains differently predisposed to HCC indicates that the genes responsible for HCC susceptibility control the amplification and/or overexpression of c-Myc, the expression of cell cycle regulatory genes, and the activity of Ras/Erk, AKT/mTOR, and of the pro-apoptotic Rassf1A/Nore1A and Dab2IP/Ask1 pathways, the methionine cycle, and DNA repair pathways in mice and rats. Comparative functional genetic studies, in rats and mice differently susceptible to HCC, showed that preneoplastic and neoplastic lesions of resistant mouse and rat strains cluster with human HCC with better prognosis, while the lesions of susceptible mouse and rats cluster with HCC with poorer prognosis, confirming the validity of the studies on the influence of the genetic predisposition to hepatocarinogenesis on HCC prognosis in mouse and rat models. Recently, the hydrodynamic gene transfection in mice provided new opportunities for the recognition of genes implicated in the molecular mechanisms involved in HCC pathogenesis and prognosis. This method appears to be highly promising to further study the genetic background of the predisposition to this cancer.

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