RESEARCH HIGHLIGHTS
Genomics Malignant rearrangements
DNA sequencing reveals how breast cancer cells rearrange their genome to create fusion genes for driving tumor development
Cancer cells often rearrange and exchange pieces of their genome to form new DNA sequences. These DNA sequences in turn express proteins that could initiate tumor development. Edison Liu at the A*STAR Genome Institute of Singapore and an international team of researchers1
have now used the latest
DNA sequencing technology to examine how the genome is reorganized in breast cancer cell lines and tumor samples obtained from breast cancer patients. The researchers identified genomic rearrangements that may lead to proteins for causing breast cancer. When two parts of the genome that are usually not connected
come into contact with each other, different gene segments may come together to form ‘fusion’ genes. By analyzing the messen- ger RNA (mRNA) from cancer cells, Liu and co-workers were able to determine which of the fusion genes were transcribed in the cells.
The team of researchers found that fusions of two full genes
were more likely to be transcribed by the cells than fusion events that brought together two gene fragments, which instead were more likely to silence the expression of the genes. The gene families whose expression was most likely to be affected by fusions in the breast cancer cells included those that play a role in cell adhesion, cell signaling and embryonic development. The researchers also determined which of the fusion mRNA
transcripts could be translated into proteins by assessing whether the fusion transcripts were found in ribosomes — cellular organ- elles that are responsible for forming proteins. Surprisingly, the researchers observed 44% of fusion mRNA
transcripts from the breast cancer cells were bound up in ribosomes. Many of these transcripts were translated into new proteins that may wreak havoc on a normal cell, leading to the induction of cancer. Liu and co-workers focused on one particular genome rear-
rangement on chromosome 17 that is known to be present in many breast cancer cells, and can bring about the formation of a fusion mRNA transcript. The researchers found that the presence of the fusion tran- script in breast cancer samples was linked to a poorer outcome
A*STAR RESEARCH OCTOBER 2011– MARCH 2012
in patients. The findings demonstrate an association between genomic rearrangements and cancer formation, which is expected to have serious implications in cancer diagnostics and treatment. The researchers plan to apply the same approach to studying the effects of fusion transcripts in other cancers. “In the next stage of our research, we will be exploring the
functional consequences of the entire constellation of fusion transcripts present in any one cancer,” says Liu.
1. Inaki, K. et al. Transcriptional consequences of genomic structural aberrations in breast cancer. Genome Research doi:10.1101/gr.113225.110
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