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.
garvan.au/
"Alcohol-dependent individuals who live alone often are separated or divorced from their spouses due to their alcoholism," noted Preuss. "Furthermore, they are significantly more often unemployed and have a poor perspective in life. This might lead to an even higher intake of alcohol and subsequently to more hopelessness, depression and social isolation. Together with their difficult socio-economic situation, often a minor event - such as trouble with the authorities or neighbors - is enough to precipitate suicidal behavior. Very often these subjects get drunk before the suicide attempt."
"Among individuals with a history of one or more suicide attempts," added Conner, "analysis of the characteristics of the most serious attempt suggests that alcohol-dependent individuals with borderline personality disorder had high intent to die, indicating that suicide attempts in this population can not be taken lightly. In other words, alcohol-dependent individuals with a borderline personality disorder are likely to be at high risk for completed suicide, in addition to the well-known fact that they are at high risk for attempted suicide."
"I hope these findings might provide some insights for clinicians on how to assess suicide risk in these double-diagnoses subjects," said Preuss. "Clinicians and personnel who have frequent contacts with these patients in outpatient clinics or community clinics should be able to offer long-term suicide prevention strategies to subjects with known risk factors. I also hope that members of the public will realize that alcohol dependence is a psychiatric disease and not a habit, that personality disorders in alcoholic subjects occur very often, and that alcoholics with comorbid conditions are at high risk for suicidal behavior."
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