Colon cancer exhibits a corresponding epigenetic pattern in mice and humans
The illustration shows a small section from the epigenetic landscape for six normal intestinal tissues (blue) as well as five intestinal tumors (red) in mice. Peaks reflect stronger epigenetic modification. Valleys display the absence of these modifications. An epigenetic tumor marker is denoted with a green rectangle. Credit: MPI for Molecular Genetics
Tumourigenesis is driven by genetic alterations and by changes in the epigenome, for instance by the addition of methyl groups to cytosine bases in the DNA. A deeper understanding of the interaction between the genetic and epigenetic mechanisms is critical for the selection of tumour biomarkers and for the future development of therapies. Human tumour specimens and cell lines however contain a plethora of genetic and epigenetic changes, which complicate data analysis. In contrast, certain mouse tumour models contain only a single genetic mutation and allow the analysis of nascent tumours. Scientists of the Max Planck Institute for Molecular Genetics in Berlin have now discovered a recurring pattern of more than 13,000 epigenetic alterations in young tumours of the mouse. This genome-wide pattern was found to be partly conserved in human colon carcinoma, and may therefor facilitate the identification of novel clinical colon cancer biomarkers for early detection.
Two kinds of molecular changes are known to trigger tumour development: one is genetic mutations – i.e. alterations in the alphabetic sequence of the DNA –activating genes that lead to uncontrolled growth of tumours, or inactivating genes that inhibit this growth. The other is epigenetic modifications, for example new distributions of methyl groups in the DNA that contribute to the genetic information in the cancer cells being interpreted differently.
Genetic and epigenetic mechanisms work together in cancer development – but little was known about how these systems mutually influence one another, and which changes first come to light. These questions can only be answered with great difficulty through investigating human tumours: the cancer is usually already several years old when diagnosed. Accordingly, the cancer cells already exhibit thousands of genetic and epigenetic changes at this stage, which complicates the analysis.
The matter is different for the corresponding polyps in mice, which the researchers can investigate considerably earlier following their formation. For this reason, scientists of the Max Planck Institute for Molecular Genetics have now pursued the question of which epigenetic changes in intestinal tumours occur first with the help of a mouse model.
"With mice, we can investigate the first changes much more easily than with humans", says Markus Morkel, who led the study. The scientists analysed the epigenetic changes in a strain of mice with a defective copy of the APC gene. This gene serves as an intestinal tumour suppressor in mice as well as in humans. Accordingly, it has lost its functionality in a majority of patients with colon cancer.
The results displayed a clear picture:The researchers recognised a recurring pattern of more than 13,000 epigenetic changes in all of the mouse tumour samples. By contrast, they did not find this pattern in healthy intestine or in intestinal stem cells, which are the cells of origin of the tumour. Since the mice –and hence the tumours– were less than three months old, the changes must have already spread shortly after the first genetic mutation in the APC gene within the tumour cells. According to the scientists, the first mutation already leads to pathological activation of numerous enzymes controlling the epigenetic mechanisms.
Remarkably, the molecular biologists discovered large parts of the tumour-specific epigenetic pattern not only in the mouse, but also in human colon cancer tissue. "These initial epigenetic changes could therefore serve as markers and significantly simplify the early diagnosis of colon tumours in the future", hopes Markus Morkel. Patients would merely have to provide a blood sample for the diagnosis and could forego an enteroscopic procedure.
More information: Christina Grimm, Lukas Chavez, Mireia Vilardell, Alexandra L. Farrall, Sascha Tierling, Julia W. Böhm, Phillip Grote, Matthias Lienhard, Jörn Dietrich, Bernd Timmermann, Jörn Walter, Michal R. Schweiger, Hans Lehrach, Ralf Herwig, Bernhard G. Herrmann & Markus Morkel, DNA-methylome analysis of mouse intestinal adenoma identifies a tumour-specific signature that is partly conserved in human colon cancer, PLOS Genetics, 2013.
Journal reference: PLoS Genetics
Provided by Max Planck Society
- Epigenetic causes of prostate cancer Sep 05, 2012 | not rated yet | 0
- Epigenetics a factor in Tasmanian devil disease Nov 07, 2012 | not rated yet | 0
- Researchers characterize epigenetic fingerprint of 1,628 people Jun 02, 2011 | not rated yet | 0
- Researchers discover one of the mechanisms that prevents the spread of colon cancer Sep 30, 2007 | not rated yet | 0
- An epigenetic difference in twins explains different risk of breast cancer Oct 17, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics 22 hours ago | 4.5 / 5 (4) | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
A known difficulty in fighting influenza (flu) is the ability of the flu viruses to mutate and thus evade various medications that were previously found to be effective. Researchers at the Hebrew University of Jerusalem have ...
1 minute ago | not rated yet | 0 |
22 May 2013, Paris, France: The Lotus Valve, a second-generation transcatheter aortic valve implantation (TAVI) device, was successfully implanted in all of the first 60 patients in results from REPRISE II reported at EuroPCR ...
3 minutes ago | not rated yet | 0
A potentially ground-breaking human drug trial is currently underway, which aims to discover whether blood pressure medication can slow or halt the progression of Alzheimer's Disease (AD). This is the latest ...
11 minutes ago | not rated yet | 0
Scientists at Newcastle University have shed new light on how the brain tunes in to relevant information.
1 hour ago | 5 / 5 (1) | 0 |
Professor Michael Jennings, Deputy Director of the Institute for Glycomics at Griffith University, was part of an international team that discovered the previously unknown pathway of how the bacterium colonizes people.
1 hour ago | 5 / 5 (1) | 0 |
(Medical Xpress)—Research by U of T Mississauga psychology professor Glenn Schellenberg reveals that two key personality traits – openness-to-experience and conscientiousness—predict better than IQ ...
1 hour ago | not rated yet | 0 |