The finding, published in The American Journal of Human Genetics, is crucial for the development of treatment options for the disease, providing new therapeutic drug targets.
Currently, the only treatment option for this disorder is the surgical removal of the tumors. However, this very invasive and painful procedure is often necessary throughout a patient's life.
As an inherited disorder, IM begins to develop during early infancy. The disorder can be present throughout the patient's life, and the tumors can grow big enough to eventually cause bone destruction, physical disability, intestinal obstruction and death.
John Martignetti, MD, PhD, led a team of researchers at the Icahn School of Medicine at Mount Sinai to perform whole-exome sequencing among 32 people who were diagnosed with IM. The patients came from nine different families.
Using this form of genome sequencing, they analyzed all protein-coding regions of the genome.
They identified two mutations in the genes "NOTCH3" and "PDGFRB".
Dr. Martignetti, said:
"We are very excited about the findings of this study, which started 10 years ago with the enrollment of the first family. The newest developments in sequencing technology have led to a new breakthrough in understanding this debilitating disease and we can therefore begin identifying drug-based treatments to save lives for some and avoiding the negative quality of life impact of extensive and repeated surgery in others."
The two genes are already targeted by the drugs imatinib and sunitinib. The researchers hope to see whether laboratory grown cells from IM tumors are susceptible to these medications.
In addition, the scientists want to determine why these two mutations cause IM.
Dr. Martignetti, said:
"If we can learn how these mutated genes get hijacked to cause cellular miscommunication, and also test existing and novel therapies to see if they shrink the tumors, we hope to improve the lives of the individuals battling this disease."
The first published example of genome-scale RNA and DNA sequencing of a tumor was provided by researchers at the BC Cancer Agency Genome Sciences Centre, the report revealed "a major breakthrough in cancer treatment".
Written by Joseph Nordqvist