(Press-News.org) A new single-cell profiling technique has mapped pre-malignant gene mutations and their effects in solid tissues for the first time, in a study led by investigators at Weill Cornell Medicine and the New York Genome Center.
The research, published Dec. 31 in Cancer Discovery, demonstrates a practical method for simultaneously measuring specific DNA mutations and gene activity in thousands of individual cells from human tissue. The technique is expected to be useful for studying pre-cancerous cells and may ultimately guide early cancer detection and preventive therapies.
“This is a technological demonstration that opens up many new avenues of scientific research and even allows us to start thinking about therapeutic strategies,” said study senior author Dr. Dan Landau, Bibliowicz Family Professor of Medicine, and a member of the Sandra and Edward Meyer Cancer Center and the Englander Institute for Precision Medicine at Weill Cornell. He is also a core member of the New York Genome Center.
The extensive presence of mutation-containing cells alongside normal cells, typically with no obvious difference between them, is known as clonal mosaicism. Now recognized as a common feature of human aging, it arises when a DNA “driver” mutation occurs in a cell, giving the cell and its progeny—called a clone—a slight but not yet cancerous growth or survival advantage.
The researchers collaborated with Mission Bio, Inc. to develop a technology called single-cell Genotype-to-Phenotype sequencing (scG2P), which allowed them to study clonal mosaicism in solid tissues—prior studies focused mostly on mosaicism in blood cells. Solid tissue samples are stored in ways that make mutational and gene activity information more challenging to access. Moreover, obtaining an accurate picture of solid tissue mosaicism typically requires profiling larger numbers of cells.
The scG2P tool works in a rapid, automated way to sensitively detect mutations across many driver genes, along with the activity of key growth and cell-state genes in each cell. It effectively can determine how certain mutations drive abnormal cell growth and survival.
The team used scG2P to study esophageal tissue samples from six older adults. They found that more than half of the 10,000+ sampled cells contained clonal driver mutations and most had a single driver mutation in a gene called NOTCH1, which normally controls cell maturation, identity, division and survival in the lining of the esophagus and other epithelial tissues in the body. The gene-activity readouts suggested that these NOTCH1 driver mutations induce clonal overgrowth by impairing normal cell development.
“In NOTCH1-mutant clones, relatively high numbers of cells get stuck in less mature developmental stages, where they stay in the tissue and continue to divide, whereas normal, mature cells move to the tissue surface and are shed,” said study first author Dr. Dennis Yuan, a postdoctoral fellow in the Landau lab.
The next most common driver-mutation gene in the samples was TP53, which makes the p53 protein, a crucial tumor suppressor that is inactivated in many cancers. TP53-mutant clones in the samples showed impaired maturation and also more frequent cell division compared to normal cells.
The findings are consistent with one of the central ideas of cancer biology: a single mutation is usually insufficient for malignancy and cancers arise from a series of mutations, which is increasingly common as we age.
“Can we target these clones in aging tissues to prevent cancer? Can we identify the types of driver mutations that are more likely to give rise to cancer and thus are worth treating? These are questions that people in the field are now asking,” Dr. Landau said.
Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, please see the profile for Dr. Dan Landau.
This research is supported by Burroughs Wellcome Fund Career Award for Medical Scientists, Vallee Scholar Award, Blood Cancer United Scholar Award and the Mark Foundation Emerging Leader Award. This work was also supported by the National Cancer Institute (R33 CA267219), the National Human Genome Research Institute and the Center of Excellence in Genomic Science (RM1HG011014) and the National Institutes of Health Common Fund Somatic Mosaicism Across Human Tissues (UG3NS132139-01). This work is supported by the Japan Agency for Medical Research and Development (AMED): The Core Research for Evolutional Science and Technology (CREST) (JP22gm1110011 to S.O.) and the Moonshot Research and Development Program (JP22zf0127009 to S.O.), AMED (JP23ck0106798 to N.K.), the Japan Society for the Promotion of Science (JSPS), Scientific Research on Innovative Areas (JP15H05909), JSPS KAKENHI (JP20H03660 to A.Y.) and the Japan Science and Technology Agency (JST): Fusion Oriented Research for disruptive Science and Technology (FOREST) Program (JPMJFR215V to N.K.) and Moonshot Research and Development Program (JPMJMS2022-25). This work was made possible by the MacMillan Family Foundation and the MacMillan Center for the Study of the Non-Coding Cancer Genome at the New York Genome Center.
END
Scientists identify pre-cancerous states in seemingly normal aging tissues
2026-01-15
ELSE PRESS RELEASES FROM THIS DATE:
Itaconate modifications: mechanisms and applications
2026-01-15
Itaconate, an endogenous mitochondrial metabolite produced by the enzyme aconitate decarboxylase 1 (ACOD1), has emerged as a central regulator of inflammation, innate immunity, and cellular stress responses. In a comprehensive review published in the Journal of Intensive Medicine by Yang et al, researchers summarize the rapidly expanding field of itaconate biology—highlighting its chemical reactivity, protein modification mechanisms, and therapeutic potential across infectious, inflammatory, autoimmune, and neurodegenerative diseases.
Itaconate and its electrophilic ...
Potential tumor-suppressing gene identified in pancreatic cancer
2026-01-15
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and begins in the cells lining the pancreatic duct. Accounting for more than 90% of all pancreatic cancers, PDAC is extremely difficult to treat and has a very high mortality rate. According to the Global Cancer Observatory 2022 report, pancreatic cancer is the sixth most common cancer in Japan, with over 47,000 new cases and more than 40,000 deaths, making it the fourth leading cause of cancer-related mortality in the country.
In search of potential treatments, Ms. Mayuka Nii, a second-year doctoral ...
Winners of the 2026 Hill Prizes announced
2026-01-15
January 15, 2026 – Dallas – TAMEST (Texas Academy of Medicine, Engineering, Science and Technology) and Lyda Hill Philanthropies today announced the recipients of the 2026 Hill Prizes. The prizes, funded by Lyda Hill Philanthropies, propel high-risk, high-reward ideas and innovations that demonstrate significant potential for real-world impact and can lead to new, paradigm-shifting paths in research.
The prizes are given in seven categories: artificial intelligence, biological sciences, engineering, medicine, physical sciences, public health and technology. They recognize and advance top Texas innovators, providing seed funding to advance groundbreaking science and highlight ...
Autonomous AI agents developed to detect early signs of cognitive decline
2026-01-15
A team of Mass General Brigham researchers has developed one of the first fully autonomous artificial intelligence (AI) systems capable of screening for cognitive impairment using routine clinical documentation. The system, which requires no human intervention or prompting after deployment, achieved 98% specificity in real-world validation testing. Results are published in npj Digital Medicine.
Alongside the publication, the team is releasing Pythia, an open-source tool that enables any healthcare system or research institution to deploy autonomous prompt optimization for their own AI screening applications.
"We didn't build a single AI model — ...
Study finds ocean impacts nearly double economic cost of climate change
2026-01-15
For the first time, a study from researchers at Scripps Institution of Oceanography at the University of California San Diego integrates climate-related damages to the ocean into the social cost of carbon— a measure of economic harm caused by greenhouse gas emissions.
When ocean damage from climate change, dubbed the “blue” social cost of carbon, is calculated, the study finds that the global cost of carbon dioxide emissions to society nearly doubles. Until now, the ocean was largely overlooked in the standard accounting of the social cost ...
Increased deciduous tree dominance reduces wildfire carbon losses in boreal forests
2026-01-15
As climate change drives more frequent and severe wildfires across boreal forests in Alaska and northwestern Canada, scientists are asking a critical question: Will these ecosystems continue to store carbon or become a growing source of carbon emissions? New research published this week shows that when forests shift from coniferous—consisting mostly of pines, spruces and larches—to deciduous—consisting mostly of birches and aspens—they could release substantially less carbon when they burn.
The National Science Foundation-funded study, led by researchers from the Center for Ecosystem Science and Society (ECOSS) at Northern Arizona University and published in ...
Researchers discover how a respiratory bacterium obtains essential lipids from the human body and targets fat-rich tissues
2026-01-15
Barcelona, January 15, 2026. A multidisciplinary team has uncovered a key mechanism that allows the human bacterium Mycoplasma pneumoniae—responsible for atypical pneumonia and other respiratory infections—to obtain cholesterol and other essential lipids directly from the human body. The discovery, published in Nature Communications, was co-led by Dr. Noemí Rotllan, from the Sant Pau Research Institute (IR Sant Pau) and the Center for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM); Dr. Marina Marcos, from the Autonomous University of Barcelona (UAB); and Dr. David Vizarraga, from the Institute of Molecular Biology ...
Locust swarms destroy crops. Scientists found a way to stop that
2026-01-15
“They’re very destructive when there's a lot of them, but one-on-one, what's not to love?” says Arianne Cease. She’s talking about locusts.
As the director of Arizona State University’s Global Locust Initiative, Cease has a healthy admiration for these insects, even as she studies ways to manage locust swarms and prevent the destruction they cause.
Locust swarms, which may conjure images of biblical plagues and ancient famines, remain a serious problem worldwide. They can destroy crops across entire regions, ruin people’s livelihoods, ...
More resources and collaboration needed to support prevention and treatment of obesity
2026-01-15
Statement Highlights:
More than one-third of adults and children in the U.S. are living with obesity. Obesity rates are highest among non-Hispanic Black children and adults, low-income families, people living in rural areas and adults with a high school education or less.
The latest research indicates that barriers to maintaining a healthy weight or participating in weight management programs include: limited access to healthy foods, lack of time to prepare meals and engage in regular physical activity, ...
Two types of underconfidence linked to anxiety and gender
2026-01-15
Women and people with anxiety are both prone to low confidence in their own abilities, but a new study by University College London (UCL) researchers has found that the two groups are prone to two distinct types of underconfidence.
When they took more time to reflect on their answers in a simple experimental task, people with anxiety grew less confident in their answers, while women who were underconfident gained confidence.
Lead author, Dr Sucharit Katyal, who completed the work as a postdoctoral researcher at the Max Planck UCL Centre ...