New ‘PiggyBac’ mutation tool to identify new cancer genes

WASHINGTON - Researchers have developed a genetic tool to speed the discovery of novel genes involved in cancer.

The system-called PiggyBac-has already been used by the team to identify cancer-causing genes.

This new development of the PiggyBac system makes it a powerful addition to the armoury of genetic methods available to researchers for picking apart the genetic causes of cancer.

The PiggyBac process involves shipping cargos of genetic material - called transposons - around the genome using an engine known as a transposase.

The team has incorporated the PiggyBac system into the mouse genome, where the transposons can jump from gene to gene, from chromosome to chromosome, disrupting or altering the activity of the genes where they land.

“Far from being destructive, this process is empowering our search for genes underlying cancer,” said Allan Bradley, senior author on the paper.

“Some genes, when disrupted, will push cells along the road to tumour development. When we look at the tumours that develop in our mice, we can search for the molecular fingerprint of the transposons in the genome; this allows us to identify the disrupted genes that are the cause.

“With the PiggyBac, it would be possible to look at specific organs, we can switch genes on and switch genes off, we can look for cancer genes across the whole genome,” he said.

The team searched for novel cancer genes in 63 mouse blood cancers.

The system opened new doors in the genome: when the researchers inspected 72 distinct locations at which their transposon had entered the genome, they found that a remarkable two-fifths of these genetic sites had never been detected before.

Before transposons researchers often used other methods, such as viruses, to cause mutations and generate tumours.

Although these have had success in identifying genetic culprits in cancers of the blood and breast, they have not been effective in other cancer types.

“These transposons have particular preferences, particular ways of working,” said Pentao Liu, from the Wellcome Trust Sanger Institute.

“While Sleeping Beauty transposons slot into the genome most comfortably according to one pattern, PiggyBac follows another.

“So, naturally, one system will find genes that another might not. What is really exciting is that we have been able to incorporate both systems into our mouse lines so that they can be used together.

“By optimising PiggyBac in this way and by sharing these tools with researchers worldwide, we can hope to drive new discovery in cancer research,” he said. (ANI)