Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
From ‘sea of mutations,’ two possible cancer links rise to the surface

From ‘sea of mutations,’ two possible cancer links rise to the surface

By analyzing data from thousands of patients, Princeton researchers led by Professor Mona Singh have identified two genetic mutations occurring at high frequencies in three types of cancer. The mutations affect amino acids in protein molecules shown in these panels. Credit: Princeton University

By analyzing data from thousands of patients, Princeton researchers have identified genetic mutations that frequently occur in people with uterine cancer, colorectal cancer or skin cancer—an important step toward using genome sequences to better understand cancer and guide new treatments.

Many genetic malfunctions are commonly found in cancers, and scientists are working to distinguish those directly involved in both the initial growth of cancer and its spread throughout the body. The complexity of both the disease and the ordinary functions of the genome have made this a difficult problem. However, researchers have been applying advances in data science to new collections of genetic data to the question of how cancer develops.

“There are numerous mutations that occur in any individual’s cancer,” said Mona Singh, senior author of the paper and a Princeton professor of computer science and the Lewis-Sigler Institute for Integrative Genomics. “A major question in cancer genomics is to figure out, from this large sea of mutations, which ones are actually causal for cancer initiation, but also for progression.”

In a study published June 28 in the journal PLOS Computational Biology, Singh’s group addressed this question by lining up mutations in a large group of genes that play key roles in gene expression regulation and other cellular processes. These genes are known as zinc finger genes because they have a protein structure that involves a zinc ion. The researchers examined mutations in these genes using the Cancer Genome Atlas, which includes more than 10,000 tumor samples from 32 cancer types.

Daniel Munro, the paper’s lead author, said the researchers were able to take advantage of the genes’ similarities to find common cancer mutations that disrupt protein structures, leading to impaired cellular functions.

“It allows us to identify patterns because we can look at many different proteins at the same time,” said Munro, a graduate student in the Lewis-Sigler Institute for Integrative Genomics. Dario Ghersi, a former postdoctoral researcher in Singh’s lab who is now an assistant professor at the University of Nebraska Omaha, was also a co-author.

Cancer cells divide rapidly and often have deficient DNA repair mechanisms, leading to high mutation rates compared to normal cells. Therefore the researchers tested whether the mutations they had detected occurred more often than would be expected by chance—an important check to evaluate the meaning of their results. They calculated the overall mutation rates for zinc finger genes in each cancer patient and found that two sites—affecting amino acids 9 and 11 in the zinc finger domain—were mutated at higher rates than this background level.

Among other control analyses, the team also compared the mutation rates at amino acids 9 and 11 to rates of “mutational signatures” known to be common across the genome in particular cancer types. Although such mutations are common in these cancers, at amino acid 9 in zinc finger domains they occurred nearly 10 times more often than would be expected by chance in uterine and colorectal cancers.

The study further showed that in other cancer types, zinc finger genes have more mutations than the genome overall. Taken together, the results are strong evidence “that zinc finger genes are major players in the gene dysregulation you see in cancers,” said Singh.

Singh said she hoped the results would help guide laboratory research and lead to progress in understanding the mechanisms of cancer.

“We’re keen to have other people follow up on this work,” she said.


Explore further:
Altered gene regulation is more widespread in cancer than expected

More information:
Daniel Munro et al. Two critical positions in zinc finger domains are heavily mutated in three human cancer types, PLOS Computational Biology (2018). DOI: 10.1371/journal.pcbi.1006290

Journal reference:
PLoS Computational Biology

Provided by:
Princeton University

About author

Related Articles