Project description:Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mutations, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.
Project description:Colibactin, a potent genotoxin of Escherichia coli, causes DNA double strand breaks (DSBs). We investigated if colibactin creates a particular DNA damage signature in infected human cells. Genomic contexts of colibactin-induced DSBs were enriched for a distinct AT-rich hexameric sequence motif. A survey of somatic mutations at the colibactin target sites of several thousand cancer genomes revealed significant enrichment of the motif in colorectal cancers. Moreover, the exact break point location corresponded with mutational hot spots in these cancers corresponding to a distinct trinucleotide signature. This work provides evidence for a role of colibactin in the etiology of human cancer.
Project description:Investigation of whole genome gene expression level changes in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Whole genome gene expression level changes have been compared in hepatocellular carcinoma cell line hepG2 in regular culture, hepG2-slug in regular culture and hepG2-slug on Matrigel. Roche NimbleGen micro-array analysis was employed to assess global genome expression in HepG2 in regular culture, HepG2-slug in regular culture and HepG2-slug on Matrigel. The results demonstrated that the up-regulated genes and the down-regulated genes increased significantly when HepG2-slug cells with VM forming ablity were cultured on Matrigel and formed VM.