Breaking News
November 15, 2018 - CityU develops first microarrayed 3D neuronal culture platform
November 15, 2018 - Expert suggests ways to control uncomfortable vaginal symptoms in diabetic women
November 15, 2018 - New edition of Red Journal focuses on roles of imaging in radiation oncology
November 15, 2018 - Doctors Aren’t Promoting Breastfeeding’s Cancer-Protection Benefit
November 15, 2018 - Technique to ‘listen’ to a patient’s brain during tumour surgery
November 15, 2018 - Seven-year-old returns to life as a “normal, healthy child” following bone marrow transplant
November 15, 2018 - AMSBIO expands range of high quality FFPE cancer cell line controls
November 15, 2018 - Exploring NMR Spectroscopy Applications through Interesting Infographics
November 15, 2018 - Chapman University wins additional $2.9 million NIH grant to study Alzheimer’s disease
November 15, 2018 - Microgel powder reduces infection and promotes healing
November 15, 2018 - Suicidal patients with prescribed access to psychotropic drugs should be closely monitored
November 15, 2018 - Nitric oxide-releasing technology shows potential to reduce healing time of diabetic foot ulcers
November 15, 2018 - Mass shootings may trigger unnecessary blood donations
November 15, 2018 - From heart disease to cancer: New study tracks shift of county death rates
November 15, 2018 - Preventing falls with new sensor technology
November 15, 2018 - Promising technology could improve detection, diagnosis of fatal ovarian cancer
November 15, 2018 - AAP updates concussion recommendations for children and teens
November 15, 2018 - Two genomic tests help identify most effective treatment for breast cancer patients
November 15, 2018 - Researchers evaluate efficacy of salivary biomarkers for early detection of oral cancer
November 15, 2018 - NIH awards $3.5 million to continue development of robotic system for treating brain tumors
November 15, 2018 - Researchers succeed in building protein nanotubes from tiny scaffolds
November 15, 2018 - Rectal bleeding
November 15, 2018 - Nasal delivery of weight-loss hormone eases breathing problems in sleeping mice
November 15, 2018 - $9.6 million grant to fund research on vascular risk factors for brain aging, dementia | News Center
November 15, 2018 - Gum disease linked with diabetes
November 15, 2018 - Study identifies unique functional brain networks associated with ASD behaviors in infancy
November 15, 2018 - EU and industry-funded project aims to personalize diabetes treatment
November 15, 2018 - NIH researchers shed light on causes of HBV-associated acute liver failure
November 14, 2018 - FDA Alert: Implanted Pumps: Safety Communication
November 14, 2018 - Weight loss & acute Porphyria
November 14, 2018 - Researchers identify three sub-types of depression
November 14, 2018 - The puzzle of a mutated gene lurking behind many Parkinson’s cases | News Center
November 14, 2018 - The mystery viruses far worse than flu
November 14, 2018 - Research highlights physical changes in the brain of self-injuring teen girls
November 14, 2018 - Speed and error rate of DNA synthesis influenced by DNA structure
November 14, 2018 - Cranberry consumption modifies impact of animal-based diet on gut health
November 14, 2018 - £500,000 grant could pave way for new antibiotic to battle against drug-resistant superbugs
November 14, 2018 - Trump Administration Finalizes Birth Control Coverage Opt-Out
November 14, 2018 - Modern life offers children almost everything they need, except daylight
November 14, 2018 - Getting better: A patient is more than a collection of numbers
November 14, 2018 - 20 Americans Die Each Day Waiting For Organs
November 14, 2018 - First bifacial molecule can invade double-stranded DNA or RNA
November 14, 2018 - Study finds lack of safety data for using flowers in cooking
November 14, 2018 - Statistical methods play key role in predicting efficacy of new drugs
November 14, 2018 - Research explores how exercise may help fight drug addiction
November 14, 2018 - Health Tip: Limit Fat, Sugar and Salt in Your Child’s Diet
November 14, 2018 - CA 19-9 Blood Test (Pancreatic Cancer): MedlinePlus Lab Test Information
November 14, 2018 - Old drug could have new use helping sick premature babies
November 14, 2018 - Surgery, not antibiotics, should remain first-line treatment for appendicitis | News Center
November 14, 2018 - Researchers to develop sports-specific classification system for blind football
November 14, 2018 - Preschool children show awake responses to naptime nonsense words
November 14, 2018 - Researchers develop innovative treatment to repair damaged brain tissues
November 14, 2018 - Survey shows negative effect of vulvovaginal atrophy symptoms on quality of life for women
November 14, 2018 - Study sheds light on mechanisms that prevent autoimmune attack
November 14, 2018 - Sleep quality found to be worse for women who undergo surgical menopause
November 14, 2018 - One-hour cognitive behavioral therapy session reduces insomnia symptoms in prisoners
November 14, 2018 - New study provides deeper insight into chromosome segregation during mitosis
November 14, 2018 - Surgical menopause leads to more disrupted sleep than natural menopause
November 14, 2018 - Inhibition of one protein clears toxic clumps seen in Parkinson’s disease, study finds
November 14, 2018 - Appendix removal is linked to lower risk of Parkinson’s
November 14, 2018 - Lifting weights for less than an hour a week may reduce cardiovascular disease risk
November 14, 2018 - Pulmonary rehabilitation rarely received by hospitalized COPD patients despite health benefits
November 14, 2018 - New anti-HER2 drug shows promising anti-tumor activity in gullet, stomach and bowel cancers
November 14, 2018 - Regular head circumference assessment of preterm babies can help identify long-term IQ problems
November 14, 2018 - Brigham investigators examine opioid use among Massachusetts adolescents, prescription trends
November 14, 2018 - Study defines biomarker in response to treatment of castration-resistant prostate cancer
November 14, 2018 - Study identifies potential therapeutic strategy for patients with clear cell renal cancer
November 14, 2018 - Bausch Health Announces U.S. Launch of Bryhali (halobetasol propionate) Lotion, 0.01%, for Plaque Psoriasis In Adults
November 14, 2018 - Alpha Fetoprotein (AFP) Tumor Marker Test: MedlinePlus Lab Test Information
November 14, 2018 - Researchers evaluate controversial treatment for Parkinson’s disease psychosis
November 14, 2018 - AI could help veterinarians code their notes
November 14, 2018 - Pre-schoolers with autism thrive in mainstream classroom settings
November 14, 2018 - Individual and work-related factors may help promote hospital physician engagement, finds study
November 14, 2018 - Complementary and alternative medicine is widely used by general population in England
November 14, 2018 - Study reveals link between tobacco availability and smoking during pregnancy
November 14, 2018 - Purdue researchers develop translucent base for silicon patches to deliver exact doses of biomolecules
November 14, 2018 - New technology based on moths and magnets could help treat genetic diseases
November 14, 2018 - Concussion-Related Biomarkers Vary Based on Sex, Race
November 14, 2018 - One more year of high school may shape waistlines later in life
November 14, 2018 - Dissecting high drug costs – Scope
Study identifies link between DNA-protein binding, cancer onset | News Center

Study identifies link between DNA-protein binding, cancer onset | News Center

image_pdfDownload PDFimage_print

Researchers at the Stanford University School of Medicine and their collaborators at other institutions have identified a link between how proteins bind to our DNA and how cancer develops. This finding may allow researchers to predict cancer pathways and long-term patient outcomes.

The research focuses on chromatin, the DNA-protein complex where all genes reside. Specifically, it evaluates chromatin’s relationship to transcription factors — proteins that play a crucial role in managing which genes are activated within cells. Certain genes are turned on or off based on how transcription factors bind to specific parts of the chromatin. The study found that these binding patterns and the resulting gene activation act like a key to different cancer typesallowing the researchers to understand the biology of cancer at its most basic level. 

A paper detailing the research was published Oct. 26 in Science. The senior authors are Howard Chang, MD, PhD, professor of dermatology and of genetics, and William Greenleaf, PhD, associate professor of genetics. Postdoctoral scholar Ryan Corces, PhD, and graduate student Jeffrey Granja share lead authorship. 

Cancer causes a massive burden on society and is among the leading causes of death worldwide. According to the National Cancer Institute, there will be more than 1.7 million new cancer cases by the end of 2018 in the United States. Our total health care expenditures for cancer care in 2014 alone was $87.8 billion — a number that continues to increase as the years go by.

However, diseases that once seemed intractable now have functional treatments, said Chang, who is also the Virginia and D.K. Ludwig Professor of Cancer Genomics. “So, with continued work, cancer is something we can actually make sense of,” he added.

A disease of genes gone awry

Corces said that cancer is “a disease of genes gone awry.” But in order to understand where these harmful genes come from, the researchers had to look inside the nucleus to the cell’s transcription process.     

Transcription occurs when the cell takes information encoded in a gene and rewrites it in the form of messenger RNA. The DNA within a cell’s nucleus is tightly wound together with certain proteins into a threadlike structure known as chromatin, and that chromatin is further coiled to form a larger structure called a chromosome. Because of this coiling, only certain areas of the chromatin sequence are accessible to the cell’s transcription machinery. When a transcription factor finds an available section of chromatin and binds to it, that region of the DNA sequence unzips, allowing transcription to occur. However, in the case of cancer, the transcription process malfunctions, resulting in a change in gene activation.   

These switches that determine gene activity were our missing component.

To understand exactly what goes wrong during this critical stage, the researchers used 410 tumor samples, representing 23 different cancer types, from The Cancer Genome Atlas and a newly developed technique called assay for transposase-accessible chromatin using sequencing, or ATAC-seq. As Chang explained, ATAC-seq is like spray-painting your DNA but only the accessible chromatin gets painted, giving researchers a fast and easy way to identify key protein-binding areas.  

One finding showed that mutations can occur within the chromatin sequence, thereby creating a new and accessible site where a transcription factor can bind. Once the protein attaches to the site, a new gene is expressed, causing significant biological changes. 

An example of this occurred with bladder cancer tissue that the researchers examined. When the team performed ATAC-seq on the tissue, they noticed that a chromatin mutation created a new protein-binding site that was associated with a strong increase in the activity of a neighboring genethat regulates cell size, motility and shape — all of which are classic factors in cancer growth. Even more interesting was that this particular mutation was not present in the other cancer tissues analyzed in the study, suggesting that different cancer types may arise from different chromatin mutations.   

“These switches that determine gene activity were our missing component,” Chang said. “We can now find how these switches are changing cancer, including mutations that make the switch get stuck in the on position.” 

The tip of the iceberg

The vast amount of genetic research is focused on the 2 percent of our DNA that is used to create proteins. In the current study, Chang wanted to explore the other 98 percent. Called the “noncoding” section, this part of our DNA is used to make crucial regulatory components that control gene behavior and activation. It also includes information that is pertinent to cancer.   

Through this work, Chang hopes to open the door to understanding the breadth of the human genome, and of cancer itself. Moving forward, the team expects far more research aimed at discovering and understanding the effects of these noncoding sequences. 

Although the team’s findings have yet to be applied in a clinical setting, the researchers believe their work will be useful in the development of better cancer prognoses, more information on patient susceptibility to cancer and new treatments that are more localized and effective.   

Beyond its potential clinical impact, Corces said he believes the research provides valuable knowledge about cancer gene regulation.“Other people are undoubtedly going to use this chromatin accessibility data to further understand how networks of genes effect cancer,” he said. 

Other Stanford co-authors of the paper are postdoctoral scholar Seung Woo Cho, PhD; graduate student Maxwell Mumbach; research associate Shadi Shams; technician Bryan Louie; research scientists Jose Seoane, PhD, and Ansuman Satpathy, PhD; and assistant professor Christina Curtis, PhD. 

Researchers from several other institutions were co-authors of the work and are listed in the paper.

Chang is a Howard Hughes Medical Institute investigator, and Greenleaf is a Chan-Zuckerberg Biohub investigator. They are both members of Stanford Bio-X, the Stanford Cancer Institute, the Stanford Neurosciences Instituteand the Stanford Child Health Research Institute

The research was supported by the National Institutes of Health (grants R35Ca209919, P50HG007735, K99AG059918, 1U24CA210974, 1U24CA210949, 1U24CA210978, 1U24CA210952, 1U24CA210989, 1U24CA210990, 1U24CA210950, 1U24CA210969 and 1U24CA210988) and the Parker Institute for Cancer Immunotherapy.

Stanford’s departments of Genetics and of Dermatology also supported this work.

Tagged with:

About author

Related Articles