Chromosome-breakage genomic instability and chromothripsis in breast cancer

Background

Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.

Results

We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.

Conclusions

Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users.     

Using the ratio of means as the effect size measure in combining results of microarray experiments

Background  

Development of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small.     

Integrative analysis of multiple gene expression profiles with quality-adjusted effect size models

Background  

With the explosion of microarray studies, an enormous amount of data is being produced. Systematic integration of gene expression data from different sources increases statistical power of detecting differentially expressed genes and allows assessment of heterogeneity. The challenge, however, is in designing and implementing efficient analytic methodologies for combination of data generated by different research groups.     

Nitrate concentrations in snow from remote areas: implication for the global NO x flux

Increased emissions of nitrogen compounds to the atmosphere by human activities have been well documented. However, in order to better quantify these anthropogenic emissions, better knowledge of natural emissions rates must be known. In addition, variation in natural emissions through time should be documented. In this note we present data collected and/or analyzed by us for NO₃ ^– in recent snow from remote regions of the world. We also summarize existing data sets from other remote regions. This is done to establish a better understanding of NO₃ ^– deposition rates in these regions as well as to add more information to our global understanding of NO₃ ^– deposition.     

Comparative use patterns of plant resources in rural areas of South Africa and Zimbabwe

Documentation of use patterns of plants across national boundaries is of relevance in understanding the importance of plant resources to livelihood strategies of different ethnic groups. Plant resources have gained prominence as a natural asset through which families derive food, firewood, income, medicines and timber, enabling particularly poor communities to achieve self-sufficiency. The objective of this study was to investigate the trends in plant usage in South Africa and Zimbabwe. An ethnobotanical investigation was conducted between January 2012 and January 2013 in the Limpopo Province, South Africa and the Midlands Province, Zimbabwe. The study used questionnaire surveys and interviews with a total of 143 participants to explore plant use patterns in South Africa and Zimbabwe. A total of 98 plant species were identified, with Zimbabwe contributing 70 species and 47 species from South Africa. The uses were classified into 15 categories, major use categories were firewood, food plants, medicine and timber. Food plant was a major plant use category in Zimbabwe, contributing 55.1%, followed by medicinal plants (36.8%), firewood (35.7%) and timber (31.6%). In contrast, firewood was the major plant use category in South Africa, contributing 18.4%, followed by food plants (17.3%), medicinal (14.3%) and timber (1.0%). Comparison of the two countries demonstrated remarkable differences in plant use patterns. The results showed that rural households in Zimbabwe were more reliant on plant resources than their counterparts in South Africa. Such a trend could be attributed to a close relationship between the local people, and their natural and agricultural environment leading to a rich knowledge base on plants, plant use and related practices. This comparative analysis strengthens the firm belief that utilization of plant resources represents an important shared heritage, preserved over the centuries, which must be exploited in order to provide further new and useful body of ethnobotanical knowledge.