Genome reorganization in different cancer types: detection of cancer specific breakpoint regions.

BACKGROUND: Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization. The development of these changes is not only a random process, but rather comprise specific DNA regions that are prone to the reorganization process. RESULTS: We have analyzed previously published SNP arrays from three different cancer types (pancreatic adenocarcinoma, breast cancer and metastatic melanoma) and from non-malignant control samples. We calculated segmental copy number variations as well as breakpoint regions. Some of these regions were not randomly involved in genome reorganization since we detected fifteen of them in at least 20% of all tumor samples and one region on chromosome 9 where 43% of tumors have a breakpoint. Further, the top-15 breakpoint regions show an association to known fragile sites. The relevance of these common breakpoint regions was further confirmed by analyzing SNP arrays from 917 cancer cell lines. CONCLUSION: Our analyses suggest that genome reorganization is common in tumorigenesis and that some breakpoint regions can be found across all cancer types, while others exclusively occur in specific entities.

SNP microarray analyses reveal copy number alterations and progressive genome reorganization during tumor development in SVT/t driven mice breast cancer.

BACKGROUND: Tumor development is known to be a stepwise process involving dynamic changes that affect cellular integrity and cellular behavior. This complex interaction between genomic organization and gene, as well as protein expression is not yet fully understood. Tumor characterization by gene expression analyses is not sufficient, since expression levels are only available as a snapshot of the cell status. So far, research has mainly focused on gene expression profiling or alterations in oncogenes, even though DNA microarray platforms would allow for high-throughput analyses of copy number alterations (CNAs). METHODS: We analyzed DNA from mouse mammary gland epithelial cells using the Affymetrix Mouse Diversity Genotyping array (MOUSEDIVm520650) and calculated the CNAs. Segmental copy number alterations were computed based on the probeset CNAs using the circular binary segmentation algorithm. Motif search was performed in breakpoint regions (inter-segment regions) with the MEME suite to identify common motif sequences. RESULTS: Here we present a four stage mouse model addressing copy number alterations in tumorigenesis. No considerable changes in CNA were identified for non-transgenic mice, but a stepwise increase in CNA was found during tumor development. The segmental copy number alteration revealed informative chromosomal fragmentation patterns. In inter-segment regions (hypothetical breakpoint sides) unique motifs were found. CONCLUSIONS: Our analyses suggest genome reorganization as a stepwise process that involves amplifications and deletions of chromosomal regions. We conclude from distinctive fragmentation patterns that conserved as well as individual breakpoints exist which promote tumorigenesis.

Cocos: Constructing multi-domain protein phylogenies.

Phylogenies of multi-domain proteins have to incorporate macro-evolutionary events, which dramatically increases the complexity of their construction.We present an application to infer ancestral multi-domain proteins given a species tree and domain phylogenies. As the individual domain phylogenies are often incongruent, we provide diagnostics for the identification and reconciliation of implausible topologies. We implement and extend a suggested algorithmic approach by Behzadi and Vingron (2006).