Nav: Home

Hackensack Meridian CDI scientists uncover signposts in DNA for cancer, disease risk

June 29, 2020

June 29, 2020 - Nutley, NJ - By sequencing entire genomes for DNA modifications, and analyzing both cancer tissues and healthy ones, Hackensack Meridian Health researchers and doctors have found what could be a key to risks for cancer and other diseases: specific locations in the DNA where those expression changes (methylation) are imbalanced, according to a new publication.

The authors, from the Center for Discovery and Innovation (CDI), Hackensack University Medical Center and its John Theurer Cancer Center (JTCC), and the National Cancer Institute-recognized Georgetown Lombardi Comprehensive Cancer Center Consortium, published their findings in the major journal Genome Biology on June 29.

The most strongly disease-relevant genetic variants can be hard to localize in widespread scanning of the genome - but by zooming in on key genetic locations associated with these DNA methylation imbalances in multiple normal and cancer tissues, the scientists report they have uncovered promising new leads beneath the broader statistical signals.

"Our dense map of allele-specific methylation (i.e., DNA methylation imbalances dictated by genetic variation) will help other scientists prioritize and focus their work on the most relevant genetic variants associated with diseases," said Catherine Do, M.D., Ph.D., assistant member of the CDI, and the first author. "Because we also dug into the mechanisms of this phenomenon to understand how it can result in disease susceptibility, our study will help identify new interesting biological pathways for personalized medicine and drug development".

"Cancer cells are gangsters, but in our approach we make them work for us in a useful way", said Benjamin Tycko, M.D., Ph.D., the CDI lab director who oversaw the study. "These 'footprints' of allele-specific methylation are more abundant in cancers than in normal tissues, but since Catherine's work has shown they are produced by the same biological pathways, we can use our dense maps to understand the beginnings of both cancers and non-cancerous diseases - such as autoimmune, neuropsychiatric, and cardiometabolic disorders."

The current study generated one of the largest high-quality datasets used in this kind of approach. Among the DNA samples studied were various tissue types from 89 healthy controls, plus 16 cancer samples from three types of tumors treated by oncologists and surgeons at the JTCC: B-cell lymphomas, multiple myeloma, and glioblastoma multiforme (a common and difficult-to-treat brain tumor).

The scientists identified a total of 15,112 allele-specific methylation sites including 1,838 sites located near statistical signals of disease susceptibility from genome-wide association studies (GWAS). These data have been made publicly available so that other scientists can test new hypotheses in "post-GWAS" studies.

Also among its novel findings, the paper reports evidence that non-coding mutations (that do not change protein sequences) "might play roles in cancer through long range regulatory effects on gene expression." One specific example cited in the paper is a mutation that causes allele-specific methylation in the TEAD1 gene, which evidence has shown becomes over-expressed in aggressive and treatment-refractory forms of multiple myeloma.

Another discovery is that some disease-relevant genetic variants can reside in "chromatin deserts," places in the DNA which few or no specific biological signals in available tissue types - but which are revealed by the footprints of allele-specific methylation and may have been active at different times of the cell history or development stages.

"This could be a key breakthrough in determining how cancer starts - and give us a better chance to treat it," said David Siegel, M.D., founding director of the Institute for Multiple Myeloma and Lymphoma at the CDI, and also the chief of the Multiple Myeloma Division at John Theurer Cancer Center at Hackensack University Medical Center, and one of the authors. "Finding non-coding mutations that cause epigenetic activation of genes such as TEAD1 in multiple myeloma can potentially help us narrow in on the most promising targets for developing new treatments."

"Advanced epigenetic research like this will drive clinical decisions in the near future," said Andre Goy, M.D., M.S., physician-in-chief for oncology at Hackensack Meridian Health and director of John Theurer Cancer Center, also an author of the paper. "Studies like this, looking at the most detailed changes of DNA methylation and gene expression, could help us solve the riddle of how cancer starts - and perhaps how to conquer it."

"I applaud this important contribution to our understanding of cancer and its underlying biology that can potentially be applied to other disease," said Louis M. Weiner, M.D., director of Georgetown Lombardi Comprehensive Cancer Center and the MedStar Georgetown Cancer Institute. "This research finding is yet more evidence of what can be achieved by bringing together investigators from different institutions and specialties."
-end-
Authors of the study from the JTCC and CDI also include David (Kar Fai) Chow, M.D., attending pathologist and medical director of the Hackensack Meridian Health Biorepository; Rena Feinman, Ph.D., an associate member of the CDI; Emmanuel Dumont, Ph.D., a research assistant member of CDI working in Dr. Tycko's epigenetics group; George J. Kaptain, M.D., director of Neuro-Oncology, Skull-Base Surgery and Radiosurgery within the Department of Neurosurgery at Hackensack University Medical Center; Samuel Goldlust, M.D., a neuro-oncologist at John Theurer Cancer Center; Nicholas Illsley, D.Phil, senior scientists in the Department of Obstetrics and Gynecology at Hackensack University Medical Center; Angelica Castano, M.D., a research associate in the Tycko lab; and Martha Salas, also of the Tycko lab. Subha Madhavan, Ph.D., chief data scientist at the Georgetown University Medical Center and director of the Innovation Center for Biomedical Informatics (ICBI) and associate professor of Oncology was another author; and other important collaborators took part from Columbia University, Johns Hopkins, and the Karolinska Institute.

Hackensack Meridian Health

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.