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Using Genetic Sequencing to Manage Cancer in Children

Using Genetic Sequencing to Manage Cancer in Children

Using Genetic Sequencing to Manage Cancer in Children

Using Genetic Sequencing to Manage Cancer in Children

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More than 10,000 new cases of cancer are expected to be diagnosed among children from birth to 14 years of age in the United States this year. More than 1,000 children will die from cancer in 2015, making it the leading cause of death from disease among children.

Cancer is caused by abnormal cells that grow out of control. It starts when a single cell has damage to its DNA that spurs it to divide without stopping, forming tumors that may spread to other tissues. Advances in DNA sequencing technologies are improving the ability to detect these genetic misspellings, leading to improved diagnosis and treatment.

A team led by Dr. Arul Chinnaiyan at the University of Michigan started a program in 2012 to examine the feasibility of including clinical sequencing information in the care of young patients with cancer. Their goal is to tailor treatment based on the genetic features of a person’s cancer. This is known as precision medicine—an approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle.

The team enrolled 102 participants (average age 10.6 years; range, 0 to 22 years) who had cancer, including leukemia and sarcoma, that didn’t respond to treatment (refractory), had returned (relapsed), or was rare. The researchers sequenced the tumor exome (the part of DNA that codes for proteins) and RNA—as well as DNA from normal tissue—in 91 participants who had enough tumor tissue for the analysis. The study was funded in part by NIH’s National Human Genome Research Institute (NHGRI) and National Cancer Institute (NCI). Results were published on September 1, 2015, in the Journal of the American Medical Association.

The findings were discussed by a group of experts who considered scientific, logistical, and ethical issues before making recommendations to families and their physicians. The group determined that 42 of the 91 patients (46%) had genomic sequence discoveries that were potentially “actionable”—they could lead to a change in cancer management. Tailored actions were carried out in 23 patients (25%). These included changes in treatment for 14 patients (15%) and genetic counseling for future risk in participants and their families for 9 (10%).

The researchers note several limitations with the study. Since there wasn’t a control group, they couldn’t assess whether the approach resulted in improved outcomes. The sequencing cost—which was covered under the research protocol—was about $6,000 per patient. The time that it took to perform the sequencing, discuss the findings, and report back to the families was lengthy, averaging about 7 to 8 weeks.

“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time. These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient,” Chinnaiyan says.