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Stat Madness 2019

Vote for Children’s National in STAT Madness

Stat Madness 2019

Children’s National Health System has been selected to compete in STAT Madness for the second consecutive year. Our entry for the bracket-style competition is “Sensitive liquid biopsy platform to detect tumor-released mutated DNA using patient blood and CSF,” a new technique that will allow kids to get better treatment for an aggressive type of pediatric brain tumor.

In 2018, Children’s first-ever STAT Madness entry advanced through five brackets in the national competition and, in the championship round, finished second. That innovation, which enables more timely diagnoses of rare diseases and common genetic disorders, helping to improve kids’ health outcomes around the world, also was among four “Editor’s Pick” finalists, entries that spanned a diverse range of scientific disciplines.

“Children’s National researchers collaboratively work across divisions and departments to ensure that innovations discovered in our laboratories reach clinicians in order to improve patient care,” says Mark Batshaw, M.D., Children’s Executive Vice President, Chief Academic Officer and Physician-in-Chief. “It’s gratifying that Children’s multidisciplinary approach to improving the lives of children with brain tumors has been included in this year’s STAT Madness competition.”

Pediatric brain cancers are the leading cause of cancer-related death in children younger than 14. Children with tumors in their midline brain structures have the worst outcomes, and kids diagnosed with diffuse midline gliomas, including diffuse intrinsic pontine glioma, have a median survival of just 12 months.

“We heard from our clinician colleagues that many kids were coming in and their magnetic resonance imaging (MRI) suggested a particular type of tumor. But it was always problematic to identify the tumor’s molecular subtype,” says Javad Nazarian, Ph.D., MSC, a principal investigator in Children’s Center for Genetic Medicine Research. “Our colleagues wanted a more accurate measure than MRI to find the molecular subtype. That raised the question of whether we could actually look at their blood to determine the tumor subtype.”

Children’s liquid biopsy, which remains at the research phase, starts with a simple blood draw using the same type of needle as is used when people donate blood. When patients with brain tumors provide blood for other laboratory testing, a portion of it is used for the DNA detective work. Just as a criminal leaves behind fingerprints, tumors shed telltale clues in the blood. The Children’s team searches for the histone 3.3K27M (H3K27M), a mutation associated with worse clinical outcomes.

“With liquid biopsy, we were able to detect a few copies of tumor DNA that were hiding behind a million copies of healthy DNA,” Nazarian says. “The blood draw and liquid biopsy complement the MRI. The MRI gives the brain tumor’s ZIP code. Liquid biopsy gives you the demographics within that ZIP code.”

Working with collaborators around the nation, Children’s National continues to refine the technology to improve its accuracy. The multi-institutional team published findings online Oct. 15, 2018, in Clinical Cancer Research.

Even though this research technique is in its infancy, the rapid, cheap and sensitive technology already is being used by people around the globe.

“People around the world are sending blood to us, looking for this particular mutation, H3K27M, ” says Lindsay B. Kilburn, M.D., a Children’s neurooncologist, principal investigator at Children’s National for the Pacific Pediatric Neuro-Oncology Consortium, and study co-author. “In many countries or centers, children do not have access to teams experienced in taking a biopsy of tumors in the brainstem, they can perform a simple blood draw and have that blood processed and analyzed by us. In only a few days, we can provide important molecular information on the tumor subtype previously only available to patients that had undergone a tumor biopsy.”

“With that DNA finding, physicians can make more educated therapeutic decisions, including prescribing medications that could not have been given previously,” Nazarian adds.

The STAT Madness round of 64 brackets opened March 4, 2019, and the championship round voting concludes April 5 at 5 p.m. (EST).

In addition to Nazarian and Dr. Kilburn, study co-authors include Eshini Panditharatna, Madhuri Kambhampati, Heather Gordish-Dressman, Ph.D., Suresh N. Magge, M.D., John S. Myseros, M.D., Eugene I. Hwang, M.D. and Roger J. Packer, M.D., all of Children’s National; Mariam S. Aboian, Nalin Gupta, Soonmee Cha, Michael Prados and Co-Senior Author Sabine Mueller, all of University of California, San Francisco; Cassie Kline, UCSF Benioff Children’s Hospital; John R. Crawford, UC San Diego; Katherine E. Warren, National Cancer Institute; Winnie S. Liang and Michael E. Berens, Translational Genomics Research Institute; and Adam C. Resnick, Children’s Hospital of Philadelphia.

Financial support for the research described in the report was provided by the V Foundation for Cancer Research, Goldwin Foundation, Pediatric Brain Tumor Foundation, Smashing Walnuts Foundation, The Gabriella Miller Kids First Data Resource Center, Zickler Family Foundation, Clinical and Translational Science Institute at Children’s National under award 5UL1TR001876-03, Piedmont Community Foundation, Musella Foundation for Brain Tumor Research, Matthew Larson Foundation, The Lilabean Foundation for Pediatric Brain Cancer Research, The Childhood Brain Tumor Foundation, the National Institutes of Health and American Society of Neuroradiology.

Debra Regier

U.S. leads the pack in medical genetics and genomic medicine

Debra Regier

Debra S. Regier, M.D., Ph.D., a pediatric geneticist who is the director of education in the Rare Disease Institute at Children’s National Health System.

It long has been recognized that traits can be passed down from parents to offspring in humans, just as occurs with other species. But medical genetics – the scientific field that covers the diagnoses and management of heritable diseases – didn’t get its start until recently. Only in the past century or so have researchers devoted significant resources to better understanding the patterns of inheritance or syndromes that have a genetic cause.

Although this research has taken place around the world, the United States is well established as a leader in this field, say authors of an article published in the July 2017 issue of Molecular Genetics & Genomic Medicine.

This article covers the history of the field, demographics of genetic conditions, legislation that relates to genetic disease and its burdens and highlights a long list of American researchers who have genetic diseases named after them. The list, comprising 86 scientists in a diverse array of fields including pediatrics, pathology, dermatology and oncology, is a testament to the devotion of these researchers to understanding a specific condition or, sometimes, group of related conditions.

Their dedication, often spanning the entirety of their career, contributed to the wealth of knowledge now available that’s improved the outcomes of many individuals with these diseases, says article co-author Debra S. Regier, M.D., Ph.D., a pediatric geneticist who is the director of education in the Rare Disease Institute at Children’s National Health System.

“Because these researchers spent their lives characterizing these disorders,” Dr. Regier says, “we can use that information when we find a child who fits the scheme of a particular disorder to tell families what they can expect – and in many instances – explain how best to treat them.”

Beyond tracking heritable disease traits through families, modern genomics also has led to the ability to recognize specific genes that cause various disorders, speeding the process of diagnosis and intervention.

“There are about 7,000 rare diseases, and sometimes it’s hard to know where to start with patients because it’s unclear which one they have,” Dr. Regier says. “By doing genetic testing, we can give families information, offer a prognosis and start treatments that have helped children who came before them with the same genetic mutation.”

Dr. Regier speculates that U.S. leadership in this field is largely due to the presence of large academic centers that are devoted to the study of genetic disorders, like Children’s National. Such centers give researchers dedicated time and space to better understand genetic diseases, both on a basic and an applied level. Despite the country’s stature as a frontrunner in this research arena, the United States has a relatively small medical genetics community, which researchers can use to their advantage.

“If I find a child with a rare genetic disorder, I can call up the world expert on this condition to share and receive information,” Dr. Regier adds. “That’s relatively rare in science, but it happens all the time in our field because we’re so small.”

Although the United States has contributed to many medical genetics and genomic medicine advances that have helped patients worldwide, the history of the field in this country wasn’t always laudable, Dr. Regier says. The article also addresses the eugenics movement during the early 20th century. For example, in 1907, Indiana became the first state to enact involuntary sterilization legislation, an effort to remove “flawed” individuals from the gene pool that was followed by similar laws in several other states. In 1924, Virginia enacted a law that allowed eugenic sterilization of people with intellectual disabilities that was upheld by the U.S. Supreme Court in 1927.

After atrocities committed by the Nazis during World War II, when the repercussions of these policies became more clear, these laws were gradually abolished.

More recent legislation, the article’s authors write, aims to protect individuals from discrimination for genetic disorders. Thus far, 35 states have laws on the books protecting against employment discrimination, and 48 states passed legislation against health insurance discrimination based on genetic information. Twenty-four states endorsed statutes that limit the use of genetic information for other types of insurance, including life, long-term care and disability.

The article is the first of a two-part series and was followed Nov. 26, 2017 by a second article addressing the current status of prenatal testing, reproductive options and reproductive law in the United States, as well as newborn screening, genetic services, rare disease registries, and education and training in genetics.

“We can take pride in our progress, while still acknowledging that we have a long way to go in this field,” Dr. Regier says.