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Retracing the history of the mutation that gave rise to cancer decades later – Science Daily

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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.

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Breathtaking NASA Image Shows a Magical ‘Sea of Dunes’ on Mars

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On Thursday, NASA released a stunning photo of a sea of dunes on Mars.

It also shows wind-sculpted lines surrounding Mars’ frosty northern polar cap.

The section captured in the shot represents an area that is 31 kilometers (19 miles) wide, NASA said. The sea of dunes, however, actually covers an area as large as Texas.

The photo is a false color image, meaning that the colors are representative of temperatures. Blue represents cooler climes, and the shades of yellow mark out “sun-warmed dunes,” the US space agency wrote.

Sea of dark dunes surrounds Mars’ northern polar cap.(NASA/JPL-Caltech/ASU)

The photo is made of a combination of images captured by the Thermal Emission Imaging System instrument on the Mars Odyssey orbiter, NASA wrote.

Captured during the period from December 2002 to November 2004, the breathtaking images have been released to mark the 20th anniversary of Odyssey.

The Mars Odyssey orbiter is a robotic spacecraft circling Mars that uses a thermal imager to detect evidence of water and ice on the planet.

It was launched in 2001, making it the longest-working Mars spacecraft in history.

Source:- ScienceAlert

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Humans actually hunted large animals and ate mostly meat for 2 millions years: study – CTV News

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TORONTO —
Despite a widespread belief that humans owe their evolution to the dietary flexibility in eating both meat and vegetables, researchers in Israel suggest that early humans were actually apex predators who hunted large animals for two million years before they sought vegetables to supplement their diet.

In a study recently published in the American Journal of Physical Anthropology, academics from Tel Aviv University in Israel and the University of Minho in Portugal examined modern biology to determine if stone-age humans were specialized carnivores or generalist omnivores.

“So far, attempts to reconstruct the diet of Stone-Age humans were mostly based on comparisons to 20th century hunter-gatherer societies,” one of the study’s authors, Miki Ben-Dor, a researcher at Tel Aviv University, said in a press release.

“This comparison is futile, however, because two million years ago hunter-gatherer societies could hunt and consume elephants and other large animals – while today’s hunter gatherers do not have access to such bounty.”

Instead, the researchers looked at approximately 400 previous scientific studies on human anatomy and physiology as well as archeological evidence from the Pleistocene period, or “Ice Age” period, which began about 2.6 million years ago, and lasted until 11,700 years ago.

“We decided to use other methods to reconstruct the diet of Stone-Age humans: to examine the memory preserved in our own bodies, our metabolism, genetics and physical build,” Ben-Dor said.

“Human behaviour changes rapidly, but evolution is slow. The body remembers.”

They discovered 25 lines of evidence from the studied papers on human biology that seem to show that earlier Homo sapiens were apex predators at the top of the food chain.

For example, the academics explained that humans have a high acidity in their stomachs when compared to omnivores or even other predators, which is important for consuming animal products.

“Strong acidity provides protection from harmful bacteria found in meat, and prehistoric humans, hunting large animals whose meat sufficed for days or even weeks, often consumed old meat containing large quantities of bacteria, and thus needed to maintain a high level of acidity,” Ben-Dor said.

Another piece of evidence, according to the study, is the structure of human fat cells.

“In the bodies of omnivores, fat is stored in a relatively small number of large fat cells, while in predators, including humans, it’s the other way around: we have a much larger number of smaller fat cells,” Ben-Dor said.

HUNTING EXPERTS

In addition to the evidence they collected by studying human biology, the researchers said archeological evidence from the Pleistocene period supports their theory.

In one example, the study’s authors examined stable isotopes in the bones of prehistoric humans as well as their hunting practices and concluded these early humans specialized in hunting large and medium-sized animals with high fat content.

“Comparing humans to large social predators of today, all of whom hunt large animals and obtain more than 70% of their energy from animal sources, reinforced the conclusion that humans specialized in hunting large animals and were in fact hypercarnivores,” the academics noted.

Ben-Dor said Stone-Age humans’ expertise in hunting large animals played a major role in the extinction of certain large animals, such as mammoths, mastodons, and giant sloths.

“Most probably, like in current-day predators, hunting itself was a focal human activity throughout most of human evolution. Other archeological evidence – like the fact that specialized tools for obtaining and processing vegetable foods only appeared in the later stages of human evolution – also supports the centrality of large animals in the human diet, throughout most of human history,” he said.

This is not to say, however, that humans during this period didn’t eat any plants. Ben-Dor said they also consumed plants, but they weren’t a major component of their diet until the end of the era when the decline of animal food sources led humans to increase their vegetable intake.

Eventually, the researchers said humans had no choice but to domesticate both plants and animals and become farmers.

Ran Barkai, one of the study’s authors and a professor at Tel Aviv University, said their findings have modern-day implications.

“For many people today, the Paleolithic diet is a critical issue, not only with regard to the past, but also concerning the present and future. It is hard to convince a devout vegetarian that his/her ancestors were not vegetarians, and people tend to confuse personal beliefs with scientific reality,” he said. 

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Marimaca Copper: First Drill Hole Intersects Broad Zone of Sulphide Copper Mineralization at Marimaca – Junior Mining Network

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VANCOUVER, British Columbia, April 07, 2021 (GLOBE NEWSWIRE) — Marimaca Copper Corp. (“Marimaca Copper” or the “Company”) (TSX: MARI) is pleased to announce the assay results of the first drill hole of a five-hole program targeting extensions of sulphide mineralization below the Company’s flagship Marimaca Oxide Deposit (“MOD”). Drilling encountered a broad zone of chalcopyrite and minor chalcocite, indicating potential for economic sulphide mineralization.

Highlights

  • Drill hole MAR-125 intersected 116m (expected approximate true width) at an average grade of 0.51% CuT from 162m, including two higher grade zones of:
    • 20m with an average grade of 0.77% CuT from 162m; and
    • 42m with an average grade of 0.92% CuT from 236m.
  • Intersection represents a significantly broader zone of mineralization than anticipated from earlier, nearby, sulphide drilling intersections
  • First drill hole of an initial five-hole campaign to test for extensions of mineralization at depth
    • First hole designed to extend mineralization closer to sulphide zones identified in historical drilling
    • Remaining four holes designed to test the limits of mineralization with step outs of approximately 300m at depth and between 400m and 700m along strike to the north and south of the first hole
  • Sulphide drilling to be completed shortly, with assay results on remaining holes expected by the end of April 2021
  • In response to escalating COVID situation in Chile, the Company has initiated a break in drilling which is not expected to impact the original target of testing all identified targets by the end of 1H 2021.

Sergio Rivera, VP Exploration of Marimaca Copper, commented:

“The results of the first hole of this initial campaign are extremely pleasing, exceeding both the widths and grades we had projected for this zone based on earlier drilling completed nearby. The broad intercept of chalcopyrite mineralization shows good continuity downhole, with potentially economic grades, especially at the bottom of the intercept.

“The drilling has also provided additional geological information, which we are using to refine our understanding of the controls of mineralization and to inform future drillhole locations, targeting mineralized extensions at depth and along strike.

“The next four holes are significant step outs from the known mineralized zones outside of the Mineral Resource Estimate area and are designed to test the limits of the mineralized body, both at depth and along strike. The second hole will be collared approximately 350m to the east of MAR-125, targeting mineralization up to 300m below the current deepest mineralization. The third, fourth and fifth holes will be located between 400m and 700m to the north and south of MAR-125, aiming to test for extensions along strike.

“This first hole has provided encouragement that there is potential for economically interesting sulphide mineralization at Marimaca, while the next four drill holes are designed to better delineate the tonnage potential of this.”

Discussion of Campaign Objectives and Results

The current five-hole drilling campaign at the Marimaca Copper Project is designed to test for extensions to mineralization below the MOD. Based on the structural controls of the mineralization, the results of previous geophysical campaigns and earlier drilling, which extended beyond the current Mineral Resource Estimate (“MRE”) area, the Company believes there is the potential for extensions of the mineralized body at depth across the full strike length of the MOD. All drill holes will be drilled at an azimuth of 270o and at -60o, roughly perpendicular to the north-south striking, easterly dipping mineralizing structures. Intercepts should, therefore, be relatively close to the true width of the mineralization.

The first drill hole (MAR-125) encountered a broad zone of dominantly chalcopyrite mineralization with some pyrite and minor chalcocite over a down hole width (expected to be equivalent to approximate true width) of 116m with an average grade of 0.51% CuT. This includes two zones of higher-grade mineralization including 20m with an average grade of 0.77% CuT and 42m with an average grade of 0.92% CuT at the end of the mineralized intercept. The hole was collared to test mineralization approximately 100m to the east of the earlier hole ATR-82, which intersected 44m of sulphide copper mineralization with an average grade of 1.05% CuT, and 200m and 300m east of holes ATR-93 and ATR-94 respectively, which both intersected mineralization with true widths of around 40m with average grades above 1.0% CuT. MAR-125 has demonstrated an extension to this higher-grade mineralization and provides further areas to target for follow up drilling.

MAR-125 is located in the center of the current MRE area, proximal to a zone of relatively high-grade sulphide mineralization intercepted in several drill holes over widths of between 30m and 50m. The remaining four drill holes have been located to test the limits of the mineralization by stepping out significantly at depth and along strike beyond the current MRE area. The collar of the second hole, MAS-03, is located approximately 100m to the south and 350m to the east of MAR-125 and is aimed to intersect mineralization approximately 300m below MAR-125. MAS-02 and MAS-04, located approximately 400m and 700m, respectively, south of MAR-125, and are planned as significant step outs along strike, targeting the conductivity high noted in the IP survey completed across the MOD

Figure 2

Sampling and Assay Protocol

True widths cannot be determined with the information available at this time. Marimaca Copper RC holes were sampled on a 2-metre continuous basis, with dry samples riffle split on site and one quarter sent to the Andes Analytical Assay preparation laboratory in Calama and the pulps then sent to the same company laboratory in Santiago for assaying. A second quarter was stored on site for reference. Samples were prepared using the following standard protocol: drying; crushing to better than 85% passing -10#; homogenizing; splitting; pulverizing a 500-700g subsample to 95% passing -150#; and a 125g split of this sent for assaying. All samples were assayed for CuT (total copper), CuS (acid soluble copper) by AAS. A full QA/QC program, involving insertion of appropriate blanks, standards and duplicates was employed with acceptable results. Pulps and sample rejects are stored by Marimaca Copper for future reference.

Qualified Person

The technical information in this news release, including the information that relates to geology, drilling and mineralization was prepared under the supervision of, or has been reviewed by Sergio Rivera, Vice President of Exploration, Marimaca Copper Corp, a geologist with more than 36 years of experience and a member of the Colegio de Geólogos de Chile and of the Institute of Mining Engineers of Chile, and who is the Qualified Person for the purposes of NI 43-101 responsible for the design and execution of the drilling program.

Mr. Rivera confirms that he has visited the Marimaca Project on numerous occasions, is responsible for the information contained in this news release and consents to its publication.

Contact Information
For further information please visit www.marimaca.com or contact:

Tavistock
+44 (0) 207 920 3150
Jos Simson/Emily Moss 
This email address is being protected from spambots. You need JavaScript enabled to view it. 

Forward Looking Statements

This news release includes certain “forward-looking statements” under applicable Canadian securities legislation. These statements relate to future events or the Company’s future performance, business prospects or opportunities. Forward-looking statements include, but are not limited to, the impact of a rebranding of the Company, the future development and exploration potential of the Marimaca Project. Actual future results may differ materially. There can be no assurance that such statements will prove to be accurate, and actual results and future events could differ materially from those anticipated in such statements. Forward-looking statements reflect the beliefs, opinions and projections on the date the statements are made and are based upon a number of assumptions and estimates that, while considered reasonable by Marimaca Copper, are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors, both known and unknown, could cause actual results, performance or achievements to be materially different from the results, performance or achievements that are or may be expressed or implied by such forward-looking statements and the parties have made assumptions and estimates based on or related to many of these factors. Such factors include, without limitation: risks related to share price and market conditions, the inherent risks involved in the mining, exploration and development of mineral properties, the uncertainties involved in interpreting drilling results and other geological data, fluctuating metal prices, the possibility of project delays or cost overruns or unanticipated excessive operating costs and expenses, uncertainties related to the necessity of financing, the availability of and costs of financing needed in the future as well as those factors disclosed in the Company’s documents filed from time to time with the securities regulators in the Provinces of British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, New Brunswick, Nova Scotia, Prince Edward Island and Newfoundland and Labrador. Accordingly, readers should not place undue reliance on forward-looking statements. Marimaca Copper undertakes no obligation to update publicly or otherwise revise any forward-looking statements contained herein whether as a result of new information or future events or otherwise, except as may be required by law.


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