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Cancer cells suppress large regions of DNA by a reversible process that can be tackled
April 24, 2006Cancer researchers at Sydney's Garvan Institute, in collaboration with Spanish scientists, have formulated a new concept for how cancer cells can escape normal growth controls, which may have far-reaching implications for the new generation of cancer therapies.
They have found large regions of DNA are 'switched off' in colon cancer. Lead researcher Associate Professor Sue Clark, of the Garvan Institute, says: "These large regions - referred to as suburbs - contain genes that normally function to prevent the development of tumours".
Our cells become cancerous when the normal controls over cell growth and death go awry. This deregulation has traditionally been linked to DNA mutations of single genes or deletion of large sections of the chromosome. However more recently it has become clear that gene silencing in cancer can also occur, in the absence of changes to the DNA sequence: a phenomenon known as 'epigenetics'. DNA methylation is one of the main epigenetic processes.
In cancer, the DNA methylation pattern of many genes changes. However, until now, it was believed that only individual single genes were silenced by methylation. But this is not necessarily the case. "What we've found is that non-methylated genes that reside in a particular suburb near methylated genes are also silenced. Their physical proximity to the methylated genes affects their ability to function. It's a case of being in the wrong neighbourhood at the wrong time", says Assoc. Professor Clark.
The Garvan team developed a new method to scan the entire complement of the 30 000 plus genes - the entire genome - in the cancer tissue samples, which allowed widespread changes to be identified in specific parts of the genome.
They were amazed to find the extent of gene silencing. Assoc. Professor Clark adds: "What we want to do now is determine if these same regions are switched off in other types of cancers".
The team also hope that new cancer therapies, which can reverse DNA methylation, will restore the cell's normal regulation and treat and prevent cancer.
Research Australia
In cancer, the DNA methylation pattern of many genes changes. However, until now, it was believed that only individual single genes were silenced by methylation. But this is not necessarily the case. "What we've found is that non-methylated genes that reside in a particular suburb near methylated genes are also silenced. Their physical proximity to the methylated genes affects their ability to function. It's a case of being in the wrong neighbourhood at the wrong time", says Assoc. Professor Clark.
The Garvan team developed a new method to scan the entire complement of the 30 000 plus genes - the entire genome - in the cancer tissue samples, which allowed widespread changes to be identified in specific parts of the genome.
They were amazed to find the extent of gene silencing. Assoc. Professor Clark adds: "What we want to do now is determine if these same regions are switched off in other types of cancers".
The team also hope that new cancer therapies, which can reverse DNA methylation, will restore the cell's normal regulation and treat and prevent cancer.
Research Australia
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