Signatures of copy number alterations in human cancer.

Gains and losses of DNA are prevalent in cancer and emerge as a consequence of inter-related processes of replication stress, mitotic errors, spindle multipolarity and breakage-fusion-bridge cycles, among others, which may lead to chromosomal instability and aneuploidy1,2. These copy number alterations contribute to cancer initiation, progression and therapeutic resistance3-5. Here we present a conceptual framework to examine the patterns of copy number alterations in human cancer that is widely applicable to diverse data types, including whole-genome sequencing, whole-exome sequencing, reduced representation bisulfite sequencing, single-cell DNA sequencing and SNP6 microarray data. Deploying this framework to 9,873 cancers representing 33 human cancer types from The Cancer Genome Atlas6 revealed a set of 21 copy number signatures that explain the copy number patterns of 97% of samples. Seventeen copy number signatures were attributed to biological phenomena of whole-genome doubling, aneuploidy, loss of heterozygosity, homologous recombination deficiency, chromothripsis and haploidization. The aetiologies of four copy number signatures remain unexplained. Some cancer types harbour amplicon signatures associated with extrachromosomal DNA, disease-specific survival and proto-oncogene gains such as MDM2. In contrast to base-scale mutational signatures, no copy number signature was associated with many known exogenous cancer risk factors. Our results synthesize the global landscape of copy number alterations in human cancer by revealing a diversity of mutational processes that give rise to these alterations.

Role of wild birds and environmental contamination in the epidemiology of Salmonella infection in an outdoor pig farm.

Foodborne outbreaks caused by Salmonella are often attributed to the pork consumption. Salmonella contamination of retail pork is directly linked to the Salmonella prevalence on farm. In UK, approximately 40% of breeding pigs are kept outdoors. Aim of this study was to investigate the role of wild birds in the epidemiology of Salmonella in one outdoor pig farm. Three sampling visits were carried out at monthly intervals to an outdoor farm consisting of two fields, one left empty of pigs for more than 2 years (field A) while the second (field B) was occupied by pigs during the first visit only. Faeces from wild bird droppings, environmental samples and pig faeces were tested for Salmonella. Salmonella spp. was isolated from environmental samples also in field A that had not been occupied by pigs more than 2 years. Interestingly, the wild bird population accessing the fields increased considerably once the pigs had left the farm and the proportion of Salmonella positive wild bird droppings increased over time with 7.4%, 15.8% and 44.3% at the first, second and third visit, respectively. The levels of Salmonella identified in some of the wild bird droppings were unusually high (105-106 CFU/g) suggesting that Salmonella was actively replicating in the gastrointestinal tract of these birds. Monophasic Salmonella Typhimurium DT193 was the predominant serotype isolated in pigs as well as in wild bird droppings and the environment, suggesting that the pigs were the original source of infection, as this serovar is typically associated with pigs.