A New Way to Decipher how Cancer Starts

Cancers arise due to spontaneous changes in DNA, which accumulate over time and cause unrestricted cell growth. The accumulation of these changes makes it challenging to ascertain which errors initiated the cancer. To bypass this problem, researchers normally introduce DNA errors into cells and use the cells as a tool to identify cancer-causing genes. Unfortunately, this strategy has only been successfully achieved using cells from zebrafish and mice. PM Senior Scientist Dr. Rama Khokha and her team have now resolved this issue using several cutting-edge genomic techniques and successfully introduced traceable genome-wide DNA errors into normal human cells.

The study used a novel combination of retroviruses and short DNA sequences (transposons) to insert DNA at random sites across the genome. This rapidly transformed the normal cells into tumour cells with DNA alterations comparable to those found in multiple human cancers. Detailed genomic analyses of these newly generated tumours yielded 80 candidate genes with the potential to drive cancer growth. Importantly, one of the genes found to be defective in at least one in ten tumours has previously been shown to suppress cell growth and is involved in regulating DNA organization.

As Dr. Khokha explains “Our results reveal the potential for using viruses and transposons to rapidly uncover new cancer-causing targets, which will accelerate the global effort to decipher the genes, pathways and networks that drive cancer development and growth.”

This work was supported by the Ontario Institute for Cancer Research, the Canadian Cancer Society Research Institute and The Princess Margaret Cancer Foundation.

Human somatic cell mutagenesis creates genetically tractable sarcomas. Molyneux SD, Waterhouse PD, Shelton D, Shao YW, Watling CM, Tang QL, Harris IS, Dickson BC, Tharmapalan P, Sandve GK, Zhang X, Bailey SD, Berman H, Wunder JS, Iszvak Z, Lupien M, Mak TW, Khokha R.
Nature Genetics. 2014 Aug 17. [Pubmed abstract]

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