A whole new level of control of cancer gene activity within tumors, has been described by researchers as ‘dark matter’.
It was recently discovered and published in two major studies at the same time in Nature that cancers can evolve to become more aggressive without relying on DNA mutations.
Testing cancers for just the DNA mutations can skip this level of control and therefore fail to predict how cancers may behave and respond to treatment, the researchers say.
Both studies revealed how a level of gene control called ‘epigenetics’ pays a central role in the progression and development of bowel cancer.
The research was led by scientists at The Institute of Cancer Research, London, Human Technopole in Milan and Queen Mary University of London. It was funded by Wellcome, the Medical Research Council (MRC) and Cancer Research UK.
Dark matter could accurately predict cancer’s behavior
The researchers say their findings could change the way cancer is thought about and the way it is treated – and lead to new forms of tests that predict cancer’s behavior more accurately.
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The chemical changes that occur to the three-dimensional structure of DNA through epigenetics, do not change the DNA code but it can control access to genes. The researchers said it has increasingly been recognized as playing a major role in the development of cancer.
The influence of epigenetic control on how bowel cancers grow and develop over time was tracked for the first time thanks to the scientists’ work. They managed to track this separately from the influence of mutations to the DNA code, which were mapped at the same time.
For every cancer they examined, the researchers noted important epigenetic changes that they noted were involved in the disease’s ability to evolve and become more aggressive.
‘Something we liken to cancer’s dark matter’
Professor Trevor Graham, director of the center for evolution and cancer at the Institute of Cancer Research, said: “We’ve unveiled an extra level of control for how cancers behave – something we liken to cancer’s ‘dark matter’. For years our understanding of cancer has focused on genetic mutations which permanently change the DNA code. But our research has shown that the way the DNA folds up can change which genes are read without altering the DNA code and this can be very important in determining how cancers behave.
“I hope our work will change the way we think about cancer and its treatment – and should ultimately affect the way patients are treated. Genetic testing for cancer mutations only gives us part of the picture about a person’s cancer – and is blind to ‘epigenetic’ changes to how genes are read. By testing for both genetic and epigenetic changes, we could, potentially, much more accurately predict which treatments will work best for a particular person’s cancer.”
The researchers collected 1,373 samples from 30 bowel cancers and looked at the epigenetic changes as the cancers evolved which was recorded in the first paper.
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Cancer evolution
They noted that epigenetic changes are highly common in cells which have become cancerous and occur around genes already known to drive cancer.
They found they are heritable, meaning they can be inherited by cells with each cell division, and that they contribute to cancer evolution and they influence how cancer cells accumulate DNA mutations.
The changes were also present in cancer cells that had survival advantages which helped them to grown more than other cells.
Survival advantages
In the second paper, the researchers were trying to understand why cancer cells within the same tumor can be so different to one another, a characteristic the researchers said, helps some cells develop survival advantages becoming resistant to cancer treatments.
The researchers, wanted to understand whether the diversity of cell types within a tumor was governed by variation in the DNA code or something else. DNA sequences in diverse samples
The researchers wanted to understand whether the diversity of cell types within a tumor is governed by variation in the DNA code, or something else. They looked at the DNA sequence in diverse samples taken from different parts of the same tumor.
They found that less than 2% of changes in the DNA code in independent areas of a tumor were associated with changes in gene activity and that variation in cancer cell characteristics throughout tumors is often governed by factors other than DNA mutations.
Specific epigenetics
The researchers point out that more work needs to be done to determine cause and effect between specific epigenetic changes and modifications to cancer behavior and their findings are observational in nature.
Together, the researchers say that the papers represent a fundamental advance in understanding cancer. They stress DNA mutations are essential for ‘setting the scene’ for a cancer’s development and the way it evolves but importantly note that much of the subsequent behavior of cancer cells is determined by other factors such as epigenetics.
The researchers believe this could help explain why DNA tests don’t always predict how cancers are going to respond to treatment in order to help doctors tailor treatments for patients more effectively. They say it could also give reason as to why some environmental exposures can cause cancer without leading to mutations in the DNA code.
DNA mutations
Professor Andrea Sottoriva, head of the computational biology research centre at human technopole in Milan, who co-led the research, said: “When we study how cancers evolve over time, we tend to look at DNA mutations, but it’s clear that epigenetic changes also enable cancer to adapt and develop a survival advantage over other cells.
“We have for the first time been able to map epigenetic changes alongside the accumulation of DNA mutations as a colorectal tumor evolves. This provides exciting opportunities to create new treatments for cancer that don’t target the effects of DNA mutations, but instead the epigenetic changes which determine how genes are read.”
‘Open’s up exciting future opportunities’
Professor Kristian Helin, chief executive of the Institute of Cancer Research, and a world leader in the study of epigenetics, said: “This (dark matter) discovery represents an exciting advance in our understanding of cancer biology. Cancer’s ability to rapidly change and evolve is a key reason why it is so hard to treat. Exactly how cancer cells do this, and the factors that control how it can adapt to evade treatment, is not well understood.
“This important work demonstrates the potential role of epigenetic regulation in the development of cancer and the complexity of its behavior. It opens exciting future opportunities to assess cancer using both genetic and epigenetic tests, and eventually to treat cancer with epigenetic-directed drugs.”
The Institution of Cancer Research is is one of the world’s most influential cancer research institutes and can now add ‘dark matter’ to its list of research achievements while it continues researching how to treat the differences between cancers.
The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.
It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.
Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”
Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.
Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.
A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.
On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.
Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”
But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”
“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.
Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.
Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.
Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.
“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.
“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”
This report by The Canadian Press was first published Sept. 13, 2024.
Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.
Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.
Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.
Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.
The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.
“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.
Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.
Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.
Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.
A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.
This report by The Canadian Press was first published Sept. 10, 2024.
