LONDON—Cancer Research U.K. scientists have discovered for the first time that DNA methylation patterns—a key process in cell development—could accurately detect early bowel cancer, according to research published in Gut.
Researchers from Cancer Research U.K.'s Cambridge Research Institute analyzed 261 tumor samples taken from patients who had either benign bowel polyps or had developed bowel cancer. Analysis revealed that the DNA methylation patterns of the SFRP2 and IGF2 genes identified and distinguished between tumors and benign polyps with an accuracy of more than 90 percent.
The failure to accurately identify the remaining approximately 10 percent could be explained by the accuracy of the pyrosequencing assays, which falls into the 10 percent margin affecting borderline cases, explains Dr. Ashraf Ibrahim of the Cambridge Research Institute. "The other reason is that we didn't account for some factors, such as genetic changes."
DNA methylation is essential for life. In healthy cells, a methyl group is tagged to DNA, where it acts as a "red light," preventing certain genes from producing proteins. But this process can go wrong in cancer cells. DNA methylation can also contribute to the cause and development of cancer by blocking important protective genes.
"The molecular signals that tell genes whether to make proteins or not can become jumbled in cancer cells. We've identified several places where this signal becomes damaged and shown this is linked to bowel cancer development," Ibrahim says. "The majority of bowel cancers develop from benign polyps that turn cancerous and this crucial research deepens our understanding of the molecular changes behind this development. This first step in detecting molecular 'flags' for bowel cancer could, one day, lead to a simple test to search DNA for the early signs of the disease."
The scientists also measured levels of an enzyme called DNMT3B, which helps add methyl groups to DNA. They found levels of the enzyme to be lower at the polyp stage with higher levels in bowel cancer. The increase in enzyme levels corresponded with the increased amount of DNA methylation and provided an explanation for these changes.
Cancer Research U.K. is among the world's leading cancer charities dedicated to saving lives through research. Dr. Lesley Walker, the organization's director of cancer information, notes that, "this important research opens the way to improve detection of bowel cancer as early as possible, when it is easier to treat successfully. Our research has played an important part in the excellent progress being made in the treatment of bowel cancer—the five-year survival rates for bowel cancer have doubled over the last 40 years."
The Cambridge team is currently conducting studies within the National Health Service (NHS) bowel cancer-screening program to take advantage of these latest findings. Depending on the outcome of the NHS studies, the go/no-go decision will be made on developing a commercially viable diagnostic product. If it's a "go," Cancer Research U.K. will work with the charity's commercialization and development arm, CRT, to identify any potential commercial opportunities, Ibrahim says.
In the past, Cancer Research U.K. has licensed MCM markers to several different diagnostic partner companies, and launched what is known as the Cancer Research U.K. stratified medicines initiative.
"We've come a long way in improving screening and developing better treatments—our scientists have been involved in testing many drugs that are used to treat bowel cancer, and they've had a key role in pinning down the genetic causes of the disease," Walker summarizes. "But there is still more to be done. Research like this is vital in our goal to develop the best methods to detect, monitor and treat cancer and improve survival."
Bowel cancer is the third most common cancer in the U.K., where about 38,610 people are diagnosed with the cancer each year. The NHS Bowel Screening Program began in England in 2006 and in Scotland in 2007. The expectation is that there could be up to 20,000 fewer deaths from bowel cancer over the next 20 years if 60 percent of those eligible were screened. The health service plans to introduce Flexi-scope, which in a recent trial of this method of detecting and removing polyps before they develop into bowel cancer is projected to cut the number of cases of bowel cancer by a third and deaths from the disease by almost half (43 percent) among those screened.
Researchers from Cancer Research U.K.'s Cambridge Research Institute analyzed 261 tumor samples taken from patients who had either benign bowel polyps or had developed bowel cancer. Analysis revealed that the DNA methylation patterns of the SFRP2 and IGF2 genes identified and distinguished between tumors and benign polyps with an accuracy of more than 90 percent.
The failure to accurately identify the remaining approximately 10 percent could be explained by the accuracy of the pyrosequencing assays, which falls into the 10 percent margin affecting borderline cases, explains Dr. Ashraf Ibrahim of the Cambridge Research Institute. "The other reason is that we didn't account for some factors, such as genetic changes."
DNA methylation is essential for life. In healthy cells, a methyl group is tagged to DNA, where it acts as a "red light," preventing certain genes from producing proteins. But this process can go wrong in cancer cells. DNA methylation can also contribute to the cause and development of cancer by blocking important protective genes.
"The molecular signals that tell genes whether to make proteins or not can become jumbled in cancer cells. We've identified several places where this signal becomes damaged and shown this is linked to bowel cancer development," Ibrahim says. "The majority of bowel cancers develop from benign polyps that turn cancerous and this crucial research deepens our understanding of the molecular changes behind this development. This first step in detecting molecular 'flags' for bowel cancer could, one day, lead to a simple test to search DNA for the early signs of the disease."
The scientists also measured levels of an enzyme called DNMT3B, which helps add methyl groups to DNA. They found levels of the enzyme to be lower at the polyp stage with higher levels in bowel cancer. The increase in enzyme levels corresponded with the increased amount of DNA methylation and provided an explanation for these changes.
Cancer Research U.K. is among the world's leading cancer charities dedicated to saving lives through research. Dr. Lesley Walker, the organization's director of cancer information, notes that, "this important research opens the way to improve detection of bowel cancer as early as possible, when it is easier to treat successfully. Our research has played an important part in the excellent progress being made in the treatment of bowel cancer—the five-year survival rates for bowel cancer have doubled over the last 40 years."
The Cambridge team is currently conducting studies within the National Health Service (NHS) bowel cancer-screening program to take advantage of these latest findings. Depending on the outcome of the NHS studies, the go/no-go decision will be made on developing a commercially viable diagnostic product. If it's a "go," Cancer Research U.K. will work with the charity's commercialization and development arm, CRT, to identify any potential commercial opportunities, Ibrahim says.
In the past, Cancer Research U.K. has licensed MCM markers to several different diagnostic partner companies, and launched what is known as the Cancer Research U.K. stratified medicines initiative.
"We've come a long way in improving screening and developing better treatments—our scientists have been involved in testing many drugs that are used to treat bowel cancer, and they've had a key role in pinning down the genetic causes of the disease," Walker summarizes. "But there is still more to be done. Research like this is vital in our goal to develop the best methods to detect, monitor and treat cancer and improve survival."
Bowel cancer is the third most common cancer in the U.K., where about 38,610 people are diagnosed with the cancer each year. The NHS Bowel Screening Program began in England in 2006 and in Scotland in 2007. The expectation is that there could be up to 20,000 fewer deaths from bowel cancer over the next 20 years if 60 percent of those eligible were screened. The health service plans to introduce Flexi-scope, which in a recent trial of this method of detecting and removing polyps before they develop into bowel cancer is projected to cut the number of cases of bowel cancer by a third and deaths from the disease by almost half (43 percent) among those screened.
