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Mystery of 'monster' cancer DNA molecules solved

18 November 2014
Appeared in BioNews 780

The creation of giant, extra chromosomes present in up to three percent of all cancers can now be explained, says a study in Cancer Cell.

The 'neochromosomes' are the result of continual stitching together of fragmented pieces of genome, say scientists, who describe them as being 'Frankenstein-like'.

These neochromosomes can consist of three times more DNA than the largest of normal chromosomes, and usually contain many additional copies of cancer-driving genes.

'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,' said Professor David Thomas, one of the leaders of the research at the Garvan Institute, Sydney.

The researchers used a combination of next-generation DNA sequencing and mathematical modelling to unveil the evolutionary history of the neochromosome in tumour cells from fat tissue. They showed that its formation is triggered when chromosomes spontaneously shatter and break up. The resulting DNA fragments then reassemble into a circular chromosome, which gets ripped apart unevenly during cell division.

Further divisions continue to feed this circular chromosome with more and more DNA in what appears to be a selective process; genes known to be important for cancer were repeated 60-100 times in the analysed neochromosomes. Blocking these genes killed off the cancer cells, highlighting a potential therapeutic target for treating cancers of the fat tissue.

Dr Andrew Wagner, from the Dana-Farber Cancer Institute in Boston, told New Scientist that he found the work 'fascinating', and likened the approach of sorting through shattered chromosomes to archaeology.

Professor Thomas emphasised the importance of using mathematical modelling in cancer research to ABC News Australia: 'We rarely get to see the original big bang that starts off the cancer. To get back to those primordial events, we have to use creative bioinformatics and computational biology techniques.'

SOURCES & REFERENCES
Cancer's 'Frankenstein' DNA mystery solved
ABC News |  11 November 2014
Monster cancer chromosome is made from shattered DNA
New Scientist |  10 November 2014
Scientists Solve Mystery of ‘Frankenstein’ DNA
Garvan Institute (press release) |  11 November 2014
The Architecture and Evolution of Cancer Neochromosomes
Cancer Cell |  10 November 2014
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