‘Frankenstein’ DNA behind cancer growth

‘Frankenstein’ DNA behind cancer growth

Pink villi
December 2014

Associate Professor Tony Papenfuss standing in front of computers
Associate Professor Tony Papenfuss

Researchers have uncovered how massive DNA molecules that appear in some tumours form like Frankenstein’s monster, stitched together from other parts of the genome.

The research solves a decades-old mystery about how these molecules, known as neochromosomes, form and explains how the tumours ensure their own survival.

Putting together the pieces

Neochromosomes are giant, extra chromosomes found in up to three per cent of all cancers, most commonly in liposarcomas (tumours of fat tissue), sarcomas (soft tissue tumours) and some brain and blood cancers.

Scientists from the Walter and Eliza Hall Institute, Peter MacCallum Cancer Centre and Garvan Institute showed that spontaneous and catastrophic chromosomal ‘explosions’ trigger formation of neochromosomes.

The shattered relics reassemble haphazardly, followed by a genetic frenzy of amplification and deletion. Genes known to be important for cancer development are massively amplified, assuring the cancer’s survival.

The researchers examined neochromosomes from liposarcomas and used mathematical modelling to reconstruct the sequence of events that caused them to form, deducing that only chromosomal shattering could be to blame.

Clues lead to cancer trigger

Institute researcher Associate Professor Tony Papenfuss said the research was like archaeology, sifting through the relics of past events to understand the present. “We showed that chromosome 12 shatters and its remnants haphazardly form a ring of DNA,” he said.

“Small circles of DNA gradually become giant circles, progressively amplifying certain genes in what appears to be a selective process. The neochromosome sucks in DNA from all parts of the genome. At a certain point, the circle stops growing and becomes a giant linear chromosome that can be seen through a microscope.”

Professor David Thomas from the Garvan Institute said the study also identified a potential therapeutic target to explore for treating liposarcomas. “When the key genes that were amplified through this process were blocked, the cancer cells died,” he said.