U.S. News & World Report - It is still in its infancy, but a genomic medicine revolution is underway in leading children's hospitals, transforming the diagnosis and treatment of a growing list of childhood ailments, researchers said Friday.
Three decades after researchers first reported genetic variations in leukemia patients that markedly influenced the course of their disease, scientists are delving deeper.
They have shown that cancers once thought to be a single disease are many – their differences decided by distinct genetic mutations. They have begun to use this information to guide treatment. And they have begun to identify and catalogue genetic variations linked to certain birth defects and to a host of subtler, hard-to-diagnose genetic diseases.
In time the approaches now being explored in a handful of top research institutions around the country will become routine in children's hospitals everywhere, researchers said Friday at the 2016 U.S. News Healthcare of Tomorrow Conference in Washington.
"Clearly we're at an early pioneering stage of using genome information with children," said Dr. Stephen Kingsmore, president and chief executive officer of Rady Children's Institute for Genomic Medicine in San Diego.
The researchers sketched the outlines of three distinctly different research programs, all geared toward using genetic information to diagnose and treat tragic childhood diseases.
Dr. James Downing, president and CEO of St. Jude Children's Research Hospital, offered an update on St. Jude's Pediatric Genome Project, a $100 million effort to study the genomes of every pediatric cancer patient seeking treatment at the institution.
"In every single pediatric cancer that we looked at, we made fundamental discoveries that changed the way we look at pediatric cancer and affected the way we diagnose and risk-stratify the disease," Downing said. Stratifying risk is the way cancer specialists determine the patient's odds of surviving the disease.
The researchers have expanded the analysis to include sequencing of so-called germ-line DNA, the DNA found in the sperm and egg and the source of all the other DNA in the body. In order to study germ-line DNA, researchers must obtain special consent and they've found that almost all patients' families are willing to supply it.
By comparing this DNA with DNA taken from the child's tumor, researchers can pinpoint abnormalities that might otherwise have been missed. "In every patient, we're identifying lesions that would have been missed," Downing said. Now the challenge is to determine what these variations mean: Do they cause disease? Do they reflect a new form of cancer? Do they offer any insights into the best approach for treatment?
Dr. F. Sessions Cole, chief medical officer at St. Louis Children's Hospital and assistant vice chancellor for children's health at Washington University in St. Louis, said his team has focused on structural birth defects in children, physical abnormalities present at birth that affect an estimated 120,000 newborns every year.In essence the team compares the baby's genetic code with the code from his or her parents to see if there are any differences that account for the problem. "We were lucky and found a couple of families whose babies had birth defects that were associated with genes that had never been found to have a human disease association before," Cole said.
In some children, the mutation is occurred spontaneously and wasn't inherited from the parents. When a gene might be passed down to another child, the parents are offered genetic counseling so that they can assess their risk of passing the gene along to another child.
Kingsmore and his colleagues at Rady have focused their attention on the small percentage of babies who land in the newborns' intensive care unit. But they cast a wide net -- testing them for 8,300 diseases that are the leading causes of death among these critically ill children. Their aim is to produce a diagnosis that helps doctors decide how best to treat the child. "The key to better outcomes is a timely diagnosis," Kingsmore said.
He offered the example of a child with liver failure, with a week to live. Faced with a choice of palliative care or agreeing to take part in a genetic analysis, the parents opted to supply all their DNA to be analyzed, along with the DNA of their child. Within 24 hours, the analysis generated information equivalent to a book 12,000 feet high, Kingsmore said.
"Within 15 minutes we can decode that information and compare it with reference genomes for babies and apply a filter to get rid of the normal stuff. Next we use algorithms to focus on those that are most likely to cause human diseases."
Ultimately, the analysis narrowed to one disease, a metabolic problem that could be treated. The baby survived. "He's a happy, healthy, 4-year-old boy," Kingsmore said.
If this approach were expanded to include all pediatric ICU patients in San Diego, he added, doctors would likely diagnose more than 150 with treatable diseases each year. Those whose diseases are found to be untreatable could be guided to palliative care – and perhaps spared unnecessary procedures including – as in one recent case – surgery.