Collaborative Australian research team solves mystery of ‘Frankenstein’ DNA
Tuesday 11 November 2014
Associate Professor Tony Papenfuss (right) with Dr Dale Garsed: Postdoctoral Researcher and first author of the paper (left), in the Peter MacCallum Cancer Centre's Molecular Genomics facility.
A team of laboratory researchers from Melbourne and Sydney have pieced together a long-held biological mystery, articulating the sequence of events that explains how grossly enlarged DNA molecules grow like Frankenstein’s monster and drive some cancers.
The researchers, from the Peter MacCallum Cancer Centre, Walter and Eliza Hall Institute of Medical Research (WEHI) and Garvan Institute of Medical Research, worked backward using complex mathematic modelling to reveal neochromosomes — massive, additional chromosomes found in the nucleus of some cancer cells — are formed when normal chromosomes shatter and get stitched back together, while undergoing genetic alterations that ensure the cell’s survival.
Associate Professor Tony Papenfuss: Head, Bioinformatics and Cancer Genomics Laboratory at Peter Mac and Laboratory Head in the Bioinformatics Division at WEHI says the findings, published overnight in Cancer Cell, shed new light on neochromosomes, which were first discovered in the 1950s and are found in three per cent of all cancers, but frequently in sarcomas.
‘Normal cells have 23 pairs of chromosomes, neat packages of genetic information, but unwelcome, additional neochromosomes are often many times larger and harbour cancer-causing oncogenes.
‘For decades scientists could not explain their creation, so this finding is exciting and carries implications for our understanding and future treatment of cancers in which neochromosomes are more common, such as liposarcomas (tumours of fat tissue), sarcomas (soft tissue tumours) and some brain and blood cancers.’
Associate Professor Papenfuss says the extent of the genetic rearrangement as parts of broken chromosomes re-form and mutate is both insidious and astonishing, yet offers new insight and hope.
‘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.
‘In a heartening aspect of this work, when we blocked the activity of key oncogenes that were massively amplified in the cancer cells, they died, which opens up new avenues of research to combat their ability to survive and thrive.’
View the research paper.
Associate Professor Tony Papenfuss and Professor David Thomas: Director, The Kinghorn Cancer Centre at the Garvan led the research team, with Dr Dale Garsed from the Peter MacCallum Cancer Centre, Dr Owen Marshall from the Murdoch Children’s Research Institute and Drs Vincent Corbin and Arthur Hsu from WEHI; the research was supported by the National Health and Medical Research Council and the Victorian Government.
- 'Scientists solve Frankenstein DNA puzzle', Herald Sun,Tuesday 11 November 2014.
- 'Australian researchers make breakthrough in sarcoma cancer research', ABC Radio The World Today, Tuesday 11 November 2014.
- 'Cancer breakthrough', Ten Eyewitness News, Tuesday 11 November 2014.
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