High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers

Scott Newman,Paul Aw Edwards

doi:10.1186/gm140

Abstract

Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome, and it is now being applied to structural changes, using the 'paired end' strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular, there are probably many fusion genes, analogous to those found in leukemias, to be found in common cancers, such as breast carcinoma, and some of these will prove to be important in cancer diagnosis and treatment.

Highlights

Somatic structural variations in the genome - referred to by cytogeneticists as translocations, inversions, duplications and insertions - can be powerful events in tumor evolution because they can create fusion genes
The BCR-ABL fusion gene defines a group of leukemias and is the target of treatment with the kinase inhibitor Glivec
In stark contrast to leukemias, lymphomas and sarcomas, in which many important oncogenes have been identified at translocation breaks, we have a poor understanding of how structural variations contribute to carcinogenesis in common epithelial tumors [1,2]

Summary

Introduction

Introduction Somatic structural variations in the genome - referred to by cytogeneticists as translocations, inversions, duplications and insertions - can be powerful events in tumor evolution because they can create fusion genes. Stephens et al [5] recently presented the first largescale survey of somatically acquired structural variation in the genomes of cancers, with the explicit goal of discovering genes disrupted and fused at chromosome breakpoints.

Results

Conclusion