- QMSat – Université de Sherbrooke
- Killick-1 – Memorial University
- VIOLET – University of New Brunswick
Live coverage of the launch will air on NASA Live.
There is no stronger risk factor for cancer than age. At the time of diagnosis, the median age of patients across all cancers is 66. That moment, however, is the culmination of years of clandestine tumor growth, and the answer to an important question has thus far remained elusive: When does a cancer first arise?
At least in some cases, the original cancer-causing mutation could have appeared as long as 40 years ago, according to a new study by researchers at Harvard Medical School and the Dana-Farber Cancer Institute.
Reconstructing the lineage history of cancer cells in two individuals with a rare blood cancer, the team calculated when the genetic mutation that gave rise to the disease first appeared. In a 63-year-old patient, it occurred at around age 19; in a 34-year-old patient, at around age 9.
The findings, published in the March 4 issue of Cell Stem Cell, add to a growing body of evidence that cancers slowly develop over long periods of time before manifesting as a distinct disease. The results also present insights that could inform new approaches for early detection, prevention, or intervention.
“For both of these patients, it was almost like they had a childhood disease that just took decades and decades to manifest, which was extremely surprising,” said co-corresponding study author Sahand Hormoz, HMS assistant professor of systems biology at Dana-Farber.
“I think our study compels us to ask, when does cancer begin, and when does being healthy stop?” Hormoz said. “It increasingly appears that it’s a continuum with no clear boundary, which then raises another question: When should we be looking for cancer?”
In their study, Hormoz and colleagues focused on myeloproliferative neoplasms (MPNs), a rare type of blood cancer involving the aberrant overproduction of blood cells. The majority of MPNs are linked to a specific mutation in the gene JAK2. When the mutation occurs in bone marrow stem cells, the body’s blood cell production factories, it can erroneously activate JAK2 and trigger overproduction.
To pinpoint the origins of an individual’s cancer, the team collected bone marrow stem cells from two patients with MPN driven by the JAK2 mutation. The researchers isolated a number of stem cells that contained the mutation, as well normal stem cells, from each patient, and then sequenced the entire genome of each individual cell.
Over time and by chance, the genomes of cells randomly acquire so-called somatic mutations — nonheritable, spontaneous changes that are largely harmless. Two cells that recently divided from the same mother cell will have very similar somatic mutation fingerprints. But two distantly related cells that shared a common ancestor many generations ago will have fewer mutations in common because they had the time to accumulate mutations separately.
Cell of origin
Analyzing these fingerprints, Hormoz and colleagues created a phylogenetic tree, which maps the relationships and common ancestors between cells, for the patients’ stem cells — a process similar to studies of the relationships between chimpanzees and humans, for example.
“We can reconstruct the evolutionary history of these cancer cells, going back to that cell of origin, the common ancestor in which the first mutation occurred,” Hormoz said.
Combined with calculations of the rate at which mutations accumulate, the team could estimate when the JAK2 mutation first occurred. In the patient who was first diagnosed with MPN at age 63, the team found that the mutation arose around 44 years prior, at the age of 19. In the patient diagnosed at age 34, it arose at age 9.
By looking at the relationships between cells, the researchers could also estimate the number of cells that carried the mutation over time, allowing them to reconstruct the history of disease progression.
“Initially, there’s one cell that has the mutation. And for the next 10 years there’s only something like 100 cancer cells,” Hormoz said. “But over time, the number grows exponentially and becomes thousands and thousands. We’ve had the notion that cancer takes a very long time to become an overt disease, but no one has shown this so explicitly until now.”
The team found that the JAK2 mutation conferred a certain fitness advantage that helped cancerous cells outcompete normal bone marrow stem cells over long periods of time. The magnitude of this selective advantage is one possible explanation for some individuals’ faster disease progression, such as the patient who was diagnosed with MPN at age 34.
In additional experiments, the team carried out single-cell gene expression analyses in thousands of bone marrow stem cells from seven different MPN patients. These analyses revealed that the JAK2 mutation can push stem cells to preferentially produce certain blood cell types, insights that may help scientists better understand the differences between various MPN types.
Together, the results of the study offer insights that could motivate new diagnostics, such as technologies to identify the presence of rare cancer-causing mutations currently difficult to detect, according to the authors.
“To me, the most exciting thing is thinking about at what point can we detect these cancers,” Hormoz said. “If patients are walking into the clinic 40 years after their mutation first developed, could we have caught it earlier? And could we prevent the development of cancer before a patient ever knows they have it, which would be the ultimate dream?”
The researchers are now further refining their approach to studying the history of cancers, with the aim of helping clinical decision-making in the future.
While their approach is generalizable to other types of cancer, Hormoz notes that MPN is driven by a single mutation in a very slow growing type of stem cell. Other cancers may be driven by multiple mutations, or in faster-growing cell types, and further studies are needed to better understand the differences in evolutionary history between cancers.
The team’s current efforts include developing early detection technologies, reconstructing the histories of greater numbers of cancer cells, and investigating why some patients’ mutations never progress into full-blown cancer, but others do.
“Even if we can detect cancer-causing mutations early, the challenge is to predict which patients are at risk of developing the disease, and which are not,” Hormoz said. “Looking into the past can tell us something about the future, and I think historical analyses such as the ones we conducted can give us new insights into how we could be diagnosing and intervening.”
Study collaborators include scientists and physicians from Brigham and Women’s Hospital, Boston Children’s Hospital, Massachusetts General Hospital, and the European Bioinformatics Institute. The other co-corresponding authors of the study are Ann Mullally and Isidro Cortés-Ciriano.
The study was supported in part by the National Institutes of Health (grants R00GM118910, R01HL158269), the Jayne Koskinas Ted Giovanis Foundation for Health and Policy, the William F. Milton Fund at Harvard University, an AACR-MPM Oncology Charitable Foundation Transformative Cancer Research grant, Gabrielle’s Angel Foundation for Cancer Research, and the Claudia Adams Barr Program in Cancer Research.
Watching the celestial event safely is possible with the right equipment and some preparation.
With the upcoming total solar eclipse on April 8, 2024, the New England College of Optometry (NECO) urges the general public to observe this celestial phenomenon safely. Solar eclipses are rare events that spark widespread interest and excitement. To ensure everyone can enjoy the eclipse without risking their vision, NECO is sharing crucial guidelines for proper viewing.
“Solar eclipses present a wonderful opportunity for communities to engage with astronomy, but it’s vital that safety is a priority,” says George Asimellis, PhD, Msc, MBA, Professor of Vision Science at NECO. “Viewing a solar eclipse without appropriate protection can result in solar retinopathy, which can cause lasting damage to the eyes. You must take proper precautions to view the eclipse.” PLEASE NOTE: NECO recommends that individuals who have recently undergone eye surgery or who have chronic eye conditions should refrain from viewing the eclipse.
NECO will host an eclipse viewing party on Monday, April 8, from 2:00-4:00pm at their main campus located at 424 Beacon Street in Boston’s Back Bay. Media are welcome to attend and receive a free pair of eclipse viewing glasses. Faculty will be present to talk about the science behind safely viewing an eclipse.
The map below (courtesy of NASA) shows the eclipse’s path of totality.
For those who reside outside the path of totality: The Boston area is outside the eclipse’s path of totality. However, we will be able to view a partial eclipse starting at about 2:10pm. Our area will experience moderate darkness and a drop in temperature during the partial eclipse, which will last two hours. Eclipse glasses must still be used to protect your eyes from the harmful rays of the sun, even during a partial eclipse!
Our vision experts are available for comment and additional information on eye care during this astronomical event. Please contact our Marketing Department by calling (617) 587-5609, or email [email protected].
For more information from national experts on the April 8 solar eclipse, visit NASA or the American Optometric Association.
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One of the largest studies on wildlife activity—involving more than 220 researchers, 163 mammal species and 5,000 camera traps worldwide—reveals that wild animals react differently to humans depending on where the animals live and what they eat.
Bigger herbivores—plant-eating animals like deer or moose—tend to become more active when humans are around, while meat-eaters like wolves or wolverines tend to be less active, preferring to avoid risky encounters.
Urban animals like deer or raccoons may become more active around people, as they get used to human presence and find food like garbage or plants, which they can access at night. But animals living farther from cities and other developed areas are more wary of encountering people.
The new study, a collaboration across researchers from 161 institutions, used data from before and during the COVID-19 lockdowns to examine wildlife behaviour amid changing human activity levels.
“COVID-19 mobility restrictions gave researchers a truly unique opportunity to study how animals responded when the number of people sharing their landscape changed drastically over a relatively short period,” said lead author Dr. Cole Burton, an associate professor of forest resources management at UBC and Canada Research Chair in Terrestrial Mammal Conservation.
“And contrary to the popular narratives that emerged around that time, we did not see an overall pattern of ‘wildlife running free’ while humans sheltered in place. Rather, we saw great variation in activity patterns of people and wildlife, with the most striking trends being that animal responses depended on landscape conditions and their position in the food chain.”
In Canada, researchers monitoring areas such as Banff and Pacific Rim national parks, Cathedral, Golden Ears and South Chilcotin Mountains provincial parks, and the Sea-to-Sky corridor in B.C. found that carnivores like wolverines, wolves and cougars were generally less active when human activity was higher.
In several of these parks, and in cities such as Edmonton, large herbivores often increased their activity but became more nocturnal with the presence of more humans. Large carnivores were notably absent from the most human-dominated landscapes.
These findings highlight the importance of measures to minimize any detrimental effects of human disturbance on wildlife, including reducing overlaps that might lead to conflict.
“In remote areas with limited human infrastructure, the effects of our actual presence on wildlife may be particularly strong. To give wild animals the space they need, we may consider setting aside protected areas or movement corridors free of human activity, or consider seasonal restrictions, like temporary closures of campsites or hiking trails during migratory or breeding seasons,” said study co-author and UBC biologist Dr. Kaitlyn Gaynor.
She added that strategies must also fit specific species and locations. In more remote areas, keeping human activity low will be necessary to protect sensitive species. In areas where people and animals overlap more, such as cities, nighttime is an important refuge for wildlife, and keeping it that way can help species survive. Efforts may focus on reducing human-wildlife conflict after dark, such as more secure storage of trash bins to reduce the number of animals getting into human food sources, or use of road mitigation measures to reduce vehicle collisions.
The findings are particularly useful amid the surge in global travel and outdoor recreation post-pandemic, Dr. Burton added.
“Understanding how wildlife respond to human activity in various contexts helps us develop effective conservation plans that have local and global impact. For that reason, we are working to improve wildlife monitoring systems using tools like the camera traps that made it possible to observe animal behaviours during the pandemic.”
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