In the news

Try and identify which of the genetic rearrangements found in breast cancer genomes are important in cancer development.

The transcriptome of 89 breast cancer cell lines and tumours were sequenced and gene fusion transcripts identified. Transcripts that might be involved in tumour development were prioritised based on the knowledge of the association of component genes with cancer. The effect of particular transcripts on cell function was investigated using cell lines.

384 expressed gene fusions were identified and 24 genes were found to be recurrent fusion partners. Gene fusions involving MAST kinase and Notch family of genes were prioritized and their functional effect investigated. Fusions involving these genes were shown to impact on the proper functioning of the breast epithelial cells, suggesting they play a role in the development of cancer.

MAST kinase and Notch gene rearrangements may be present in up to 5–7% of breast cancers and could be a cause of disease.  Such recurrent gene rearrangements have an important role to play in subsets of carcinomas and are potential targets for therapy. Transcriptome sequencing could be a means of identifying individuals with rare, targetable gene fusions. 

Cancer genomes are extremely complex and identifying those rearrangements that are causal is a difficult task. An understanding of mutations which are important in tumour development and progression is important for the development of improved diagnostics and therapy.