ChondroGene Limited (TSX Venture: CDG - News) announced today that two abstracts have been accepted for presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting being held in Atlanta from June 2 to 6. The two abstracts detail results of the Company's work in identifying blood-based biomarkers for colon cancer and for prostate cancer. Both abstracts demonstrate the power and flexibility of the Sentinel Principle(TM), ChondroGene's proprietary approach to identify molecular signatures of disease in blood.
The first abstract entitled, "Novel blood biomarker panel detects human colorectal cancer" was authored by M. Han, C. T. Liew, H. W. Zhang, K. T. Yip, Z. Y. Song, H. M. Li, X. P. Geng, L. X. Zhu, K. W. Marshall, C. C. Liew. ChondroGene scientists worked with researchers at the Chinese University of Hong Kong, Hong Kong, China, Lam Wah Ee Hospital, Penang, Malaysia, The 2nd Affiliated Hospital of Zhejiang University, Hangzhou, China and Anhui Medical University, Hefei, China. The abstract reports results from a study that identified gene signatures from blood cells which were then used to identify and characterize a set of biomarkers able to differentiate patients with colorectal cancer from controls.
The second abstract entitled "Blood-based biomarkers for detecting aggressive prostate cancer at time of biopsy" was authored by R. K. Nam, K. W. Marshall, R. Zheng, H. W. Zhang, S. A. Narod, C. C. Liew. This study, conducted with research collaborators at the University of Toronto, identified a set of blood biomarkers that were able to distinguish patients with aggressive forms of prostate cancer from controls.
"We are pleased that our two abstracts were accepted for presentation at this conference. The annual ASCO meeting is an important international conference where many new cancer diagnostic and therapeutic innovations and discoveries are first disclosed," stated K. Wayne Marshall, MD, PhD, President and CEO of ChondroGene. "We, along with our collaborators, are very encouraged by our initial results in colon and prostate cancer detection using blood samples. We continue to collect additional patient samples and conduct further studies in order to refine our tests in these two areas as we prepare to commercialize our first products."
Wednesday, April 26, 2006
Tuesday, April 25, 2006
A Better Way To Gauge Prostate Cancer Risk?
A team of American researchers has developed a "risk calculator" that they say is a better tool for predicting a man's odds of developing prostate cancer than prostate-specific antigen blood testing alone.
The calculator - posted online for use by both patients and physicians - adds age, race, family history of prostate cancer, prior biopsy findings and digital rectal exam results into the mix alongside PSA levels to assess a man's risk before having a new biopsy.
"PSA is a very important predictor of cancer, but is only one part of the picture of a man's risk of cancer," explains study author Dr. Ian M. Thompson, professor and chairman of the department of urology at the University of Texas Health Science Center in San Antonio.
His team describes the new screen in the April issue of the Journal of the National Cancer Institute.
According to the American Cancer Society, prostate cancer is the second leading cancer killer for men. An estimated one in six men will receive a prostate cancer diagnosis in their lifetime, and more than 30,000 Americans currently die of the disease each year.
For healthy men over the age of 50, the ACS now recommends an annual PSA blood test, as well as a digital rectal exam. The organization advises that men at higher risk -- such as blacks and patients with a history of prostate cancer in their family -- begin such testing at age 45.
While 50 percent of older men now undergo routine PSA screenings, Thompson says his prior work suggests that PSA results are more useful when taken in context with other factors. Too often, he says, PSA levels are interpreted as black-and-white indicators of either "normal" or "elevated" risk status. The truth is that rising PSA levels reflect a more graduated increase in cancer risk.
Looking for a more accurate method, Thompson and his colleagues collected data from more than 5,500 healthy men over the age of 55 who had participated in a large-scale prostate cancer prevention trial.
For a period of seven years, all the men underwent annual PSA and digital rectal exam testing, and well as having at least one prostate biopsy conducted over the study period. By the study's end, nearly 22 percent of the men went on to develop prostate cancer, and 5 percent developed high-grade disease.
At the seven-year mark, the researchers fed a combination of accumulated data -- biopsy findings, patient age, race, family history of prostate cancer, previous biopsy history, along with PSA levels and DRE results - into their "statistical risk models."
Thompson's team found that a family history of prostate cancer, or an abnormal result from the PSA or DRE test, were all strongly associated with an increased risk for prostate cancer.
Race and age also figured in the equation, with blacks and older men at relatively high risk for prostate cancer.
Having had a prior negative biopsy result was found to be associated with a decreased risk for the disease.
By compiling such patient variables together, the Texas group say they were able to develop a prostate risk calculator that provides better predictive accuracy than an analysis of PSA levels alone.
"This study provides a way to integrate other important risk factors to allow men and their doctors to better understand their risk and make a more intelligent decision whether to proceed with further testing," Thompson says.
But in an accompanying editorial, Dr. H. Ballentine Carter, of the Johns Hopkins School of Medicine, cautioned that the calculator's current design fails to distinguish between slow-growing cancers and more life-threatening varieties.
This, he says, could lead to a rash of unnecessary biopsies.
Robert Smith, director of cancer screening at the American Cancer Society, says the new model has its pros and cons.
"It does not distinguish between significant and not-significant disease, so the calculator provides some help, but not enough help," he says. "But it also allows an individual to take their PSA level and actually interpret it in the context of some other information based on the experience of a large number of men, to understand what is the likelihood that they have prostate cancer. So I think it could actually be useful."
A second study, also published in the April of the same journal, suggests that new prostate cancer treatments currently undergoing clinical trials could be better and more quickly assessed by tracking ongoing changes in patients' PSA levels, rather than by waiting to tally long-term patient survival.
The team of Columbia University researchers working at New York-Presbyterian Hospital/Columbia in New York City based their conclusions on an analysis of the progress of 551 men undergoing a new treatment for prostate cancer.
They found that a 30 percent drop in PSA levels in the first three months of treatment correlated with a 50 percent drop in their risk of death -- a "surrogate" marker that could be used in place of the usual endpoint, survival. Use of this marker might mean a treatment's effectiveness could be evaluated much earlier.
The researchers noted that the U.S. Food and Drug Administration currently bases its "endpoint" assessment of a given treatment's success solely on long-term patient survival.
The calculator - posted online for use by both patients and physicians - adds age, race, family history of prostate cancer, prior biopsy findings and digital rectal exam results into the mix alongside PSA levels to assess a man's risk before having a new biopsy.
"PSA is a very important predictor of cancer, but is only one part of the picture of a man's risk of cancer," explains study author Dr. Ian M. Thompson, professor and chairman of the department of urology at the University of Texas Health Science Center in San Antonio.
His team describes the new screen in the April issue of the Journal of the National Cancer Institute.
According to the American Cancer Society, prostate cancer is the second leading cancer killer for men. An estimated one in six men will receive a prostate cancer diagnosis in their lifetime, and more than 30,000 Americans currently die of the disease each year.
For healthy men over the age of 50, the ACS now recommends an annual PSA blood test, as well as a digital rectal exam. The organization advises that men at higher risk -- such as blacks and patients with a history of prostate cancer in their family -- begin such testing at age 45.
While 50 percent of older men now undergo routine PSA screenings, Thompson says his prior work suggests that PSA results are more useful when taken in context with other factors. Too often, he says, PSA levels are interpreted as black-and-white indicators of either "normal" or "elevated" risk status. The truth is that rising PSA levels reflect a more graduated increase in cancer risk.
Looking for a more accurate method, Thompson and his colleagues collected data from more than 5,500 healthy men over the age of 55 who had participated in a large-scale prostate cancer prevention trial.
For a period of seven years, all the men underwent annual PSA and digital rectal exam testing, and well as having at least one prostate biopsy conducted over the study period. By the study's end, nearly 22 percent of the men went on to develop prostate cancer, and 5 percent developed high-grade disease.
At the seven-year mark, the researchers fed a combination of accumulated data -- biopsy findings, patient age, race, family history of prostate cancer, previous biopsy history, along with PSA levels and DRE results - into their "statistical risk models."
Thompson's team found that a family history of prostate cancer, or an abnormal result from the PSA or DRE test, were all strongly associated with an increased risk for prostate cancer.
Race and age also figured in the equation, with blacks and older men at relatively high risk for prostate cancer.
Having had a prior negative biopsy result was found to be associated with a decreased risk for the disease.
By compiling such patient variables together, the Texas group say they were able to develop a prostate risk calculator that provides better predictive accuracy than an analysis of PSA levels alone.
"This study provides a way to integrate other important risk factors to allow men and their doctors to better understand their risk and make a more intelligent decision whether to proceed with further testing," Thompson says.
But in an accompanying editorial, Dr. H. Ballentine Carter, of the Johns Hopkins School of Medicine, cautioned that the calculator's current design fails to distinguish between slow-growing cancers and more life-threatening varieties.
This, he says, could lead to a rash of unnecessary biopsies.
Robert Smith, director of cancer screening at the American Cancer Society, says the new model has its pros and cons.
"It does not distinguish between significant and not-significant disease, so the calculator provides some help, but not enough help," he says. "But it also allows an individual to take their PSA level and actually interpret it in the context of some other information based on the experience of a large number of men, to understand what is the likelihood that they have prostate cancer. So I think it could actually be useful."
A second study, also published in the April of the same journal, suggests that new prostate cancer treatments currently undergoing clinical trials could be better and more quickly assessed by tracking ongoing changes in patients' PSA levels, rather than by waiting to tally long-term patient survival.
The team of Columbia University researchers working at New York-Presbyterian Hospital/Columbia in New York City based their conclusions on an analysis of the progress of 551 men undergoing a new treatment for prostate cancer.
They found that a 30 percent drop in PSA levels in the first three months of treatment correlated with a 50 percent drop in their risk of death -- a "surrogate" marker that could be used in place of the usual endpoint, survival. Use of this marker might mean a treatment's effectiveness could be evaluated much earlier.
The researchers noted that the U.S. Food and Drug Administration currently bases its "endpoint" assessment of a given treatment's success solely on long-term patient survival.
Friday, April 14, 2006
High cholesterol levels could boost prostate cancer risk
Men with high cholesterol levels have a 50 per cent higher risk of prostate cancer, says Italian research.
High cholesterol levels, hypercholesterolaemia, have a long association with many diseases, particularly cardiovascular disease. The link with prostate cancer is backed up by only limited evidence.
Over half a million men worldwide are diagnosed with prostate cancer every year, with over 200,000 deaths from the disease. The lowest incidence of the cancer is in Asia and the Far East, in particular India, Japan and China.
The new study, published on-line in the Annals of Oncology (doi: 10.1093/annonc/mdl080), reported: "The present study found a direct association between hypercholesterolaemia and prostate cancer, which has been only sporadically reported previously."
The case-control study, led by Francesca Bravi from the Istituto di Ricerche Farmacologiche Mario Negri in Milan, investigated cholesterol levels of 1294 men with clinically diagnosed prostate cancer, and 1451 controls with no prostate cancer.
Medical histories were obtained by self-reporting methods, not verified by using medical records, using a questionnaire. Despite the cases and controls being interviewed in hospital by trained interviewers, the self-reporting is a weakness in the study.
Results were adjusted to allow for possible confounding factors, such as body mass index, smoking habits, alcohol consumption, and family history of the disease.
After taking into account these possible complicating factors, the researchers found that hypercholesterolaemia was associated with a 50 per cent increase in the risk of prostate cancer.
The risk is even higher for hypercholesterolaemic men over 65, who increase their risk of the cancer by 80 per cent, whereas younger men had a 32 per cent increased risk.
The researchers suggest that the increased risk is linked to higher levels of prostate specific antigen (PSA), a protein that is used as a marker for the disease, in men with high cholesterol levels. Raised levels of PSA are indicative of prostate cancer risk, although two-thirds of men with high PSA levels will not have prostate cancer.
Some experts argue against the cholesterol-PSA link, saying that the metabolic products of cholesterol are carcinogenic and that this may be the mechanism responsible.
Chris Hiley, head of policy for the UK's Prostate Cancer Charity said that the study was very interesting, and may help explain why Western, developed countries with had such high incidences of the disease.
"It also suggests that if men make lifestyle changes and adopt a healthy, low cholesterol diet it might reduce their risk of prostate cancer.
"Further research is needed to confirm this, but in the meantime the health benefits of a varied diet are indisputable. We encourage men to cut down their intake of fatty foods and red and processed meat, but continue to eat oily fish and a high fibre diet with porridge oats, as well as plenty of fresh fruit and vegetables daily," she added.
Food industry executives polled by Reuters Business Insight last year predicted that by 2009, cholesterol-lowering foods would be the most profitable health food, far ahead of recently trendy products such as low-carb foods.
High cholesterol levels, hypercholesterolaemia, have a long association with many diseases, particularly cardiovascular disease. The link with prostate cancer is backed up by only limited evidence.
Over half a million men worldwide are diagnosed with prostate cancer every year, with over 200,000 deaths from the disease. The lowest incidence of the cancer is in Asia and the Far East, in particular India, Japan and China.
The new study, published on-line in the Annals of Oncology (doi: 10.1093/annonc/mdl080), reported: "The present study found a direct association between hypercholesterolaemia and prostate cancer, which has been only sporadically reported previously."
The case-control study, led by Francesca Bravi from the Istituto di Ricerche Farmacologiche Mario Negri in Milan, investigated cholesterol levels of 1294 men with clinically diagnosed prostate cancer, and 1451 controls with no prostate cancer.
Medical histories were obtained by self-reporting methods, not verified by using medical records, using a questionnaire. Despite the cases and controls being interviewed in hospital by trained interviewers, the self-reporting is a weakness in the study.
Results were adjusted to allow for possible confounding factors, such as body mass index, smoking habits, alcohol consumption, and family history of the disease.
After taking into account these possible complicating factors, the researchers found that hypercholesterolaemia was associated with a 50 per cent increase in the risk of prostate cancer.
The risk is even higher for hypercholesterolaemic men over 65, who increase their risk of the cancer by 80 per cent, whereas younger men had a 32 per cent increased risk.
The researchers suggest that the increased risk is linked to higher levels of prostate specific antigen (PSA), a protein that is used as a marker for the disease, in men with high cholesterol levels. Raised levels of PSA are indicative of prostate cancer risk, although two-thirds of men with high PSA levels will not have prostate cancer.
Some experts argue against the cholesterol-PSA link, saying that the metabolic products of cholesterol are carcinogenic and that this may be the mechanism responsible.
Chris Hiley, head of policy for the UK's Prostate Cancer Charity said that the study was very interesting, and may help explain why Western, developed countries with had such high incidences of the disease.
"It also suggests that if men make lifestyle changes and adopt a healthy, low cholesterol diet it might reduce their risk of prostate cancer.
"Further research is needed to confirm this, but in the meantime the health benefits of a varied diet are indisputable. We encourage men to cut down their intake of fatty foods and red and processed meat, but continue to eat oily fish and a high fibre diet with porridge oats, as well as plenty of fresh fruit and vegetables daily," she added.
Food industry executives polled by Reuters Business Insight last year predicted that by 2009, cholesterol-lowering foods would be the most profitable health food, far ahead of recently trendy products such as low-carb foods.
Tuesday, April 11, 2006
Tesco claims tomato will help fight prostate cancer
A TOMATO containing high levels of an antioxidant that may cut prostate cancer risk is to be launched in the UK.
Tesco says its new "healthy living" tomato contains roughly a third more lycopene than other vine varieties.
Its launch is part of the chain's move into "functional foods", which are developed to have added health benefits. The new variety was naturally bred in Holland using different tomato types with high lycopene levels.
It was then grown near Chichester, West Sussex.
A Tesco spokesman said lycopene had been linked with a potential reduction in the risk of prostate cancer.
Tesco says its new "healthy living" tomato contains roughly a third more lycopene than other vine varieties.
Its launch is part of the chain's move into "functional foods", which are developed to have added health benefits. The new variety was naturally bred in Holland using different tomato types with high lycopene levels.
It was then grown near Chichester, West Sussex.
A Tesco spokesman said lycopene had been linked with a potential reduction in the risk of prostate cancer.
Monday, April 10, 2006
16-Gene Signature Predicts Prostate Cancer Relapse: Presented at AACR
A new gene expression assay appears to be a better predictor of relapse and disease-free survival than the Gleason score in patients who have undergone prostatectomy for prostate cancer, researchers report.
Tracy M. Downs, MD, assistant clinical professor of surgery, Department of Urology, University of California, San Diego, United States, presented the findings at a press conference here on April 3rd in a poster session at the 97th Annual Meeting of the American Association for Cancer Research (AACR).
"It's a real problem to stratify prostate cancer patients who have a Gleason score of 6 or 7 after surgery," Dr. Downs said during a press conference held to announce the findings. "Half of patients with these scores do well, and the other half don't, but we cannot now predict who will fall into those groups."
In an attempt to move beyond Gleason scores, Dr. Downs and colleagues profiled formalin-fixed, paraffin-embedded samples of prostate carcinoma using an oligo-probe set for 512 prioritized genes with read-out on universal fiber optic bead arrays.
Tissue samples were obtained from 74 patients, retrieved from the VA San Diego Healthcare System a median of 44 months after surgery. Samples were excluded if patients received adjuvant therapy or if there was residual cancer in the prostate after resection.
From this the researchers identified 16 genes that are predictive of relapse, said Jian-Bing Fan, PhD, director of scientific research, Illumina, Inc, San Diego, California, United States. Illumina, Inc. is developing the assay and funded the research.
The gene expression signature is based on 11 genes that correlated positively and 5 genes that correlated negatively with Gleason scores obtained from histological examination (R =.63).
"This gene expression score seems to work much better than the Gleason score," Dr. Fan said. "Using it, we were able to stratify patients into 2 very distinct groups, 1 that has a 75% chance of relapse and 1 that only has a 20% chance of relapse."
Further study to validate the assay is planned.
Tracy M. Downs, MD, assistant clinical professor of surgery, Department of Urology, University of California, San Diego, United States, presented the findings at a press conference here on April 3rd in a poster session at the 97th Annual Meeting of the American Association for Cancer Research (AACR).
"It's a real problem to stratify prostate cancer patients who have a Gleason score of 6 or 7 after surgery," Dr. Downs said during a press conference held to announce the findings. "Half of patients with these scores do well, and the other half don't, but we cannot now predict who will fall into those groups."
In an attempt to move beyond Gleason scores, Dr. Downs and colleagues profiled formalin-fixed, paraffin-embedded samples of prostate carcinoma using an oligo-probe set for 512 prioritized genes with read-out on universal fiber optic bead arrays.
Tissue samples were obtained from 74 patients, retrieved from the VA San Diego Healthcare System a median of 44 months after surgery. Samples were excluded if patients received adjuvant therapy or if there was residual cancer in the prostate after resection.
From this the researchers identified 16 genes that are predictive of relapse, said Jian-Bing Fan, PhD, director of scientific research, Illumina, Inc, San Diego, California, United States. Illumina, Inc. is developing the assay and funded the research.
The gene expression signature is based on 11 genes that correlated positively and 5 genes that correlated negatively with Gleason scores obtained from histological examination (R =.63).
"This gene expression score seems to work much better than the Gleason score," Dr. Fan said. "Using it, we were able to stratify patients into 2 very distinct groups, 1 that has a 75% chance of relapse and 1 that only has a 20% chance of relapse."
Further study to validate the assay is planned.
Thursday, April 06, 2006
Scientists see progress in prostate cancer tests
Two companies have developed genetic tests that eventually could help doctors better predict which prostate cancer patients have serious cases that need aggressive treatment, U.S. researchers reported on Wednesday.
One test, developed by San Diego-based Illumina Inc., was designed to help physicians tell which patients considered at medium risk will have their cancer recur after the prostate is removed. Those patients typically have a score of six or seven on the 10-point Gleason scale that is among the standard tests for prostate cancer.
Researchers used the Illumina test to analyze prostate cancer tissue samples for 16 genes and studied how patients fared. They said they could use the information to give patients a score indicating whether they were likely to experience a recurrence of cancer within the next five years.
If confirmed in future studies, "this information could be used to make the next leap as to what (treatment) a patient should or should not have," said Dr. Tracy Downs, a urologic oncologist at the University of California at San Diego.
Another test developed by Berlin-based Epigenomics AG detected a gene called PITX2 and its "methylation," a chemical alteration that controls how active a gene is. The PITX2 gene is thought to play a role in regulating hormones, which can fuel cancer growth.
Men whose tissue samples tested positive on the Epigenomics test were three times more likely to experience cancer recurrence after having their prostate removed, researchers said.
"Those are the people that are really possibly good candidates for early (post-surgical) therapy," said Susan Cottrell, a senior scientist at Epigenomics's Seattle-based U.S. unit.
The company plans to seek Food and Drug Administration approval of the test if its effectiveness is confirmed in a larger study, Cottrell said. The test could be available for use in patients "in another couple years," she added.
Findings on both tests were released at a meeting of the American Association for Cancer Research.
Neither test was designed to replace the Gleason score or the PSA test that doctors typically use to determine the severity of prostate cancer, the researchers said.
Prostate cancer is the most common cancer in U.S. men. It is diagnosed in 232,000 men every year and kills up to 30,000 of them. Worldwide, 221,000 men die from prostate cancer each year.
One test, developed by San Diego-based Illumina Inc., was designed to help physicians tell which patients considered at medium risk will have their cancer recur after the prostate is removed. Those patients typically have a score of six or seven on the 10-point Gleason scale that is among the standard tests for prostate cancer.
Researchers used the Illumina test to analyze prostate cancer tissue samples for 16 genes and studied how patients fared. They said they could use the information to give patients a score indicating whether they were likely to experience a recurrence of cancer within the next five years.
If confirmed in future studies, "this information could be used to make the next leap as to what (treatment) a patient should or should not have," said Dr. Tracy Downs, a urologic oncologist at the University of California at San Diego.
Another test developed by Berlin-based Epigenomics AG detected a gene called PITX2 and its "methylation," a chemical alteration that controls how active a gene is. The PITX2 gene is thought to play a role in regulating hormones, which can fuel cancer growth.
Men whose tissue samples tested positive on the Epigenomics test were three times more likely to experience cancer recurrence after having their prostate removed, researchers said.
"Those are the people that are really possibly good candidates for early (post-surgical) therapy," said Susan Cottrell, a senior scientist at Epigenomics's Seattle-based U.S. unit.
The company plans to seek Food and Drug Administration approval of the test if its effectiveness is confirmed in a larger study, Cottrell said. The test could be available for use in patients "in another couple years," she added.
Findings on both tests were released at a meeting of the American Association for Cancer Research.
Neither test was designed to replace the Gleason score or the PSA test that doctors typically use to determine the severity of prostate cancer, the researchers said.
Prostate cancer is the most common cancer in U.S. men. It is diagnosed in 232,000 men every year and kills up to 30,000 of them. Worldwide, 221,000 men die from prostate cancer each year.
Wednesday, April 05, 2006
Another Gene Rearrangement Involved In Prostate Cancer Identified
Researchers at the University of Michigan Medical School have identified a third gene involved in prostate cancer, expanding their groundbreaking announcement, published last October in Science, that the majority of prostate cancers carry a malignancy-inducing fusion of genes never before seen in solid tumors. The new findings appear in the April 1 issue of Cancer Research. Since prostate cancer is a cancer of the epithelial cells lining organs, lead researcher Arul Chinnaiyan and his colleagues believe it likely that other gene re-arrangements may be responsible for other cancers of epithelial tissue, including breast, colon and lung.
Scott Tomlins, a MD/PhD graduate student in Dr. Chinnaiyan's laboratory and the lead author of the Science paper, presented the study Tuesday, April 4, at Experimental Biology 2006 in San Francisco. The presentation was part of the scientific program of the American Society for Investigative Pathology (ASIP) held at Experimental Biology, and Mr. Tomlins is the winner of the 2006 ASIP Experimental Pathologist-in-Training Award.
The ETV4 gene is a member of the same family as the two other genes, ETV1 and ERG, reported earlier. All three are ETS genes, a group of approximately 30 genes that encode related transcription factors. Like other family members, ETV4 has a role in normal cell division but is unusually active, or overly expressive, only when it becomes fused with other genes on different chromosomes. Using the same technology as the earlier study, the scientists were able to demonstrate that the ETV4 gene had become fused with another prostate cancer gene on another chromosome.
But the new ETV4 gene has two important differences from the ETV1 and ERG genes. First, while not overexpressed in individuals without prostate cancer, ETV4 is overexpressed in a much smaller fraction of patients with prostate cancer than the malignancy-causing genes described earlier. Second, the over-expressed ETV4 gene appeared in two prostate cancer patients in whom the ETV1 and ERG genes were not overexpressed, suggesting that fusions involving any of the three family members may lead to prostate cancer.
This finding confirms the importance of the ETS gene pathway in causing prostate cancer, say Chinnaiyan and Tomlins. The scientists believe fusions involving these three genes probably account for the majority of prostate cancers.
Citing the power of modern technology, including large gene databases (this study mined the Oncomine database, created by the Chinnaiyan laboratory, for ETS expression in two studies, one from the Chinnaiyan laboratory and the other from Stanford University), bioinformatics approaches that allow the rapid processing of previously unimaginable amounts of information, and an algorithm also created in the Chinnaiyan laboratory, the scientists will continue to look at other components of the ETS pathway, including genes that may get turned on inappropriately but may not be able to be detected through over-expression. Dr. Chinnaiyan also has plans to look for similar gene rearrangements in other solid tumors such as breast cancer.
Scott Tomlins, a MD/PhD graduate student in Dr. Chinnaiyan's laboratory and the lead author of the Science paper, presented the study Tuesday, April 4, at Experimental Biology 2006 in San Francisco. The presentation was part of the scientific program of the American Society for Investigative Pathology (ASIP) held at Experimental Biology, and Mr. Tomlins is the winner of the 2006 ASIP Experimental Pathologist-in-Training Award.
The ETV4 gene is a member of the same family as the two other genes, ETV1 and ERG, reported earlier. All three are ETS genes, a group of approximately 30 genes that encode related transcription factors. Like other family members, ETV4 has a role in normal cell division but is unusually active, or overly expressive, only when it becomes fused with other genes on different chromosomes. Using the same technology as the earlier study, the scientists were able to demonstrate that the ETV4 gene had become fused with another prostate cancer gene on another chromosome.
But the new ETV4 gene has two important differences from the ETV1 and ERG genes. First, while not overexpressed in individuals without prostate cancer, ETV4 is overexpressed in a much smaller fraction of patients with prostate cancer than the malignancy-causing genes described earlier. Second, the over-expressed ETV4 gene appeared in two prostate cancer patients in whom the ETV1 and ERG genes were not overexpressed, suggesting that fusions involving any of the three family members may lead to prostate cancer.
This finding confirms the importance of the ETS gene pathway in causing prostate cancer, say Chinnaiyan and Tomlins. The scientists believe fusions involving these three genes probably account for the majority of prostate cancers.
Citing the power of modern technology, including large gene databases (this study mined the Oncomine database, created by the Chinnaiyan laboratory, for ETS expression in two studies, one from the Chinnaiyan laboratory and the other from Stanford University), bioinformatics approaches that allow the rapid processing of previously unimaginable amounts of information, and an algorithm also created in the Chinnaiyan laboratory, the scientists will continue to look at other components of the ETS pathway, including genes that may get turned on inappropriately but may not be able to be detected through over-expression. Dr. Chinnaiyan also has plans to look for similar gene rearrangements in other solid tumors such as breast cancer.
Subscribe to:
Posts (Atom)