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Scientists solve 'Frankenstein' DNA puzzle

Scientists solve 'Frankenstein' DNA puzzle
Photo: Scientists solve 'Frankenstein' DNA puzzle
Researchers have discovered how cancer cells accumulate extra copies of cancer-causing genes, stitching together DNA to form giant chromosomes.

Australian scientists have solved the mystery of how huge, cancer-associated DNA molecules that occur in some cancers are formed.

They describe how these molecules - or neochromosomes - are made like Frankenstein's monster, sewn together from other parts of the genome.

Neochromosomes, which are usually not found in normal cells, were first discovered in the 1950s, but how they are formed was unknown to researchers until now.

"We were looking at these really strange chromosomes that exist in about three per cent of cancers," said Associate Professor Tony Papenfuss, of the Walter and Eliza Hall Institute of Medical Research in Melbourne.

The study was published in the journal Cancer Cell.

Neochromosomes are common in sarcomas (soft tissue tumours) and liposarcomas (tumours of fat tissue). They are also found in some brain and blood cancers.

"We isolated them, took the DNA out of these cells and then we sequenced them," Prof Papenfuss said.

"We sort of sifted through the details of these sequences and what we found was that these chromosomes are made up of bits of all the other chromosomes stuck together."

The researchers then used mathematical modelling to figure out how these neochromosomes were formed.

Co-author Professor David Thomas, director of The Kinghorn Cancer Centre at the Garvan Institute, said he was surprised by the extent of genetic rearrangement.

"These cancers manipulate the normal replication process in an ingenious way, creating a monster that can selectively steal and amplify the genes it needs to grow and survive," he said.

The study also identified a possible new therapeutic target for treating liposarcomas, Prof Thomas said.

"When the key oncogenes that were massively amplified in the cancer cells were blocked, the cancer cells died," he said.

Copyright AAP 2014.


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