Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

What it might take to unravel the 'lean mean machine' that is cancer

24.02.2010
Scientists from Sydney's Garvan Institute of Medical Research have published a paper, online today in Nature Cell Biology, describing gene expression in a prostate cancer cell: more sweeping, more targeted and more complex than we could ever have imagined, even five years ago.

The study shows that changes within the prostate cancer cell 'epigenome' (biochemical processes that target DNA and affect gene expression) alter the expression of many genes, silencing their expression within large regions of DNA – nearly 3% of the cell's genome.

Epigenetic 'events' include 'DNA methylation' and 'chromatin modification'. Methylation occurs when a methyl group - one carbon atom and three hydrogen atoms - attaches to a gene, determining the extent to which it is 'switched on' or 'switched off'. Chromatin, responsible for the physical coiling or structuring of DNA, can determine whether or not a gene is accessible for interaction with other molecules inside a cell.

Project leader Professor Susan Clark describes the typical cancer cell as a 'lean mean machine'. "Epigenetic changes reduce the available genome to a point where only the genes that promote cell proliferation are accessible in the cancer cell," she said.

"We can see that the epigenome is remodelled in a very consistent and precise way, effectively swamping the expression of any gene that goes against the cancer cell's interests."

"The swamping encompasses tumour suppressor genes, and all the neighbouring genes around them, as well as non-coding RNA, intergenic regions and microRNAs. Only those genes essential for growth activation are allowed to be active, while all the genes and regions that apply brakes are inactivated."

"We now have an epigenomic map of the prostate cancer cell – which we didn't have before. That has taken three years to develop, including the technology and methods to interpret our tissue samples."

"The map tells us that the tumour cell is very different from the healthy cell. It also tells us that it works in a programmed rather than a random way, and that it targets a significant part of the genome, rather than just single genes."

"It tells us that treating cancer will be far more complex than we imagined, as it will first involve understanding and reversing epigenetic change."

The findings are timely in that they coincide with very recent events and publications that have brought the concepts of the 'epigenome' and 'epigenetics' into world focus. In January 2010 the International Human Epigenome Consortium (IHEC) was launched in Paris (with Professor Clark on the interim steering Committee). Time magazine ran a feature on epigenetics in January, and Nature published two articles on the subject this month: one addressing the importance of IHEC and the urgency of pooling international mind power and resources; the other describing the infinite complexity of the project – orders of magnitude more challenging than the Human Genome Project.

The ultimate aim of IHEC is to produce a map of the human epigenome. The initial intention is to map 1,000 epigenomes within a decade. This will provide a healthy tissue base against which to compare the epigenomes of diseased tissue.

The Human Genome Project, completed in March 2000, found that the human genome contains around 25,000 genes. It took 3 billion US dollars to map them. 1

We do not yet know how many variations the human epigenome is likely to contain – certainly millions – as a single person could have many epigenomes in a lifetime, or even in a day. 2 The technological advances and computational power necessary to map the epigenome, therefore, remain incalculable.

The project at Garvan involved an initial bioinformatics phase; a comparative tissue analysis phase; and a data analysis phase.

The bioinformatics phase analysed publicly available microarray datasets (glass slides containing fragments of every gene across the genome) that had been done on prostate cancer.

Dr Warren Kaplan, Bioinformatics Analyst at Garvan's Peter Wills Bioinformatics Centre, developed new techniques to analyse the microarray data. "We designed a computer program which used a 'sliding window' – a window that computationally moves along the genome, noting the number of genes inside that window and how many of them are downregulated," he said.

"Some of the microarrays we used only measured mRNA – or the level of gene expression. Others measured the overall methylation status of the genes in that same region. It was an opportunity for us to examine the genome in a multi-layered way."

Once Kaplan had provided an initial map, Drs Marcel Coolen and Clare Stirzaker and Jenny Song from Professor Clark's lab found a way to treat and analyse prostate cancer cells, allowing their comparative DNA methylation and chromatin states analysis against the microarray data.

Bioinformaticians within the Clark lab, Aaron Statham and Dr Mark Robinson, then developed novel methodologies to interpret resulting data – essentially tens of millions of numbers. "It was like cracking a code," said Aaron. "At first the data made no sense."

Professor Clark emphasises the importance of developing the new genome technology and knowhow that allows analysis of epigenetic processes.

"There is so much we still don't know," she said. "Already we have an idea of the complexity and how it might impact on the specific drug combinations that you will have to use to reactivate genes, non-coding RNAs and microRNAs within these cancer-affected regions."

"Now that we have a prostate cancer epigenome map, our next step will be to understand the mechanism that's driving the chromatin reduction, or genome reduction within these 'lean mean machines'. In other words, what's the link between the genetics and the epigenetics?"

Footnotes

1. Time Magazine, January 18, 2010
2. Nature, Volume 463, 4 February 2010
ABOUT GARVAN
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff. Garvan's main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation and Neuroscience. Garvan's mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan's discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

MEDIA ENQUIRIES

Alison Heather
Science Communications Manager
Garvan Institute of Medical Research
+61 2 9295 8128
+61 434 071 326
a.heather@garvan.org.au

Alison Heather | EurekAlert!
Further information:
http://www.garvan.org.au

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>