An international team of scientists led by the Icahn School of Medicine at Mount Sinai and UConn School of Medicine have reported the results of a genome sequencing study for an extremely rare form of cancer. Their findings demonstrate the utility of this approach to open the door for therapy options for rare diseases that are neglected due to scarcity of patients or lack of resources. The paper was published today by JCI Insight, a journal of the American Society for Clinical Investigation.

For this project, leading genomic scientists from Mount Sinai, UConn School of Medicine, and other global collaborating institutions performed exome sequencing on tumors and matched normal samples from 17 patients with parathyroid carcinoma, an ultra-rare form of cancer for which there is no effective treatment. When a tumor forms on one of the four small parathyroid glands located behind the thyroid, it can impact the body’s control of calcium levels in both blood and bones. Patients with this cancer, if it is not cured early by surgery, typically die from its progressive metabolic complications including very high blood calcium levels, weakened bones, and calcium-induced kidney damage.

The study combined the power of UConn’s world-renowned research expertise in parathyroid disease and other endocrine tumors with Mount Sinai’s leadership in next-generation genomic sequencing and bioinformatics analysis, along with key contributions from the global consortium they organized.

Researchers found several mutations in known cancer-related genes and pathways, including the CDC73 tumor suppressor, the PI3K/AKT/mTOR pathway, and the Wnt canonical pathway, among others. This in-depth characterization provides a clear view of genetic mechanisms involved in parathyroid carcinoma and could lead to the first therapy options for patients.

“This is the largest genomic sequencing study to date for this rare and deadly cancer, and we believe it serves as important validation for using this approach to uncover clinically relevant information in any number of neglected diseases,” said Rong Chen, senior author of the paper and Assistant Professor in the Department of Genetics and Genomic Sciences at Mount Sinai. “Genomic analysis is opening the doors to diseases that could never have been understood through traditional biomedical research because there simply aren’t enough patients to observe.”

The genetic variants identified in this study have been detected in other cancers and are the subject of ongoing basket trials, or clinical trials focused on specific mutations rather than the tissue where the cancer formed.

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