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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>