CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
William Check, PhD
May 2016—Newer gene sequencing methods based on massively parallel technology have enabled much deeper penetration into DNA composition, revealing nucleotide base alterations with a sensitivity never before attainable. While next-generation sequencing has yielded substantial clinical benefits, NGS results need to be interpreted carefully.
Newer gene sequencing methods based on massively parallel technology have enabled much deeper penetration into DNA composition, revealing nucleotide base alterations with a sensitivity never before attainable. While next-generation sequencing has yielded substantial clinical benefits, NGS results need to be interpreted carefully.
Dr. Biesecker
That was illustrated by a session on somatic overgrowth syndromes, which are caused by genetic mosaicism, at the 2015 Association for Molecular Pathology meeting, where Leslie Biesecker, MD, presented on the underlying pathogenesis of such syndromes. “My key message,” Dr. Biesecker tells CAP TODAY, “was that genetic and molecular testing has become confused over the years. Diseases caused by changes in DNA are often inherited but they aren’t always inherited. And when they are not inherited they can be just as important.” Cancer is primarily a disease of noninherited somatic mutation, notes Dr. Biesecker, who is chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute.
But there is no reason to think this phenomenon is limited to cancer, he adds. “And in fact it is probably a contributor to many diseases. Now that we have newer tools, we as clinicians and clinical pathologists need to be thinking about noninherited ways that genetic change can cause disease. And one is mosaicism.”
Marilyn M. Li, MD, a professor of pathology and laboratory medicine at the University of Pennsylvania, spoke in the session about the use of NGS to detect mosaic genetic alterations underlying overgrowth syndromes. Only in recent years, she says, has there been an understanding that somatic mutations may cause diseases other than cancer. “These genetic diseases can be seen in postnatal or prenatal onset. . . . We would like to have people be aware of somatic mutations that can cause genetic diseases,” says Dr. Li, vice chief of the Division of Genomic Diagnostics and director of cancer genomic diagnostics at Children’s Hospital of Philadelphia.