New England Journal of Medicine

Scientists Pave Path for Tackling Rare Cancers

An earlier study by Dr. Andrew Arnold (center) provided the basis for the new research on parathyroid carcinoma genes.

An earlier study by Dr. Andrew Arnold (center) provided the basis for the new research on parathyroid carcinoma genes.


An international team of scientists led by the UConn School of Medicine and Icahn School of Medicine at Mount Sinai sequenced a genome for an extremely rare form of cancer, demonstrating the utility of this approach in opening the door for therapy options for rare diseases that are neglected due to scarcity of patients or lack of resources.

The team’s findings were published by JCI Insight, a journal of the American Society for Clinical Investigation.

Leading genomic scientists from UConn, Mount Sinai, and other 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.

Researchers found several mutations in known cancer-related genes and pathways. 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.

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.

“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.”

Mount Sinai’s work built upon research by Dr. Andrew Arnold of UConn, published in the New England Journal of Medicine in 2003. In the earlier study, Arnold reported on the first gene discovered in non-familial parathyroid cancer.

“Some of the tumor-specific genomic vulnerabilities we found turn out to be shared with much more common cancers, so drugs already being developed for other cancers may prove valuable in parathyroid cancer,” said Arnold, the study’s co-leader, who serves as the Murray-Heilig Chair in Molecular Medicine, director of the Center for Molecular Medicine, and chief of endocrinology at UConn School of Medicine. “This offers new hope for our patients and serves as a model for approaching other rare and neglected diseases.”

The study was funded by the Icahn Institute of Genomics and Multiscale Biology at Mount Sinai and the Murray-Heilig Fund in Molecular Medicine at UConn School of Medicine through the UConn Foundation.

UConn Health research image of a parathyroid gland (darker) located on the thyroid gland (pink background) during a research experiment where scientists genetically engineered mouse models, knocking out the CDC73 gene to test if cancer would then develop.

UConn Health research image of a parathyroid gland (darker) located on the thyroid gland (pink background) during a research experiment where scientists genetically engineered mouse models, knocking out the CDC73 gene to test if cancer would then develop.

The Power of MRI

A UConn Health physician is seen reviewing an MRI brain scan.

A UConn Health physician is seen reviewing an MRI brain scan. At UConn Health, doctors are pioneering ways to use MRI technology to diagnose and monitor a range of conditions affecting many parts of the body Photo: Peter Morenus


Magnetic resonance imaging (MRI) has come a long way since the technique was first used in the U.S. in the late 1970s. UConn Health is now taking this powerful, non-invasive imaging tool to the next level.

UConn Health physicians in a variety of specialties are using the technology — which captures images of the inside of the body using a large magnet rather than radiation — in new ways to detect and monitor illnesses.

Prostate Cancer

Dr. Peter Albertsen, chief of UConn Health’s Division of Urology, currently follows 100 patients with localized prostate cancer, which is slow-growing, using advanced multiple-parametric MRI imaging. The technology has now replaced ultrasound as the imaging method of choice for prostate cancer. The technique yields multiple imaging sequences of the prostate, providing information about the anatomy, cellular density measurement, and vascular supply.

There is growing evidence to support the idea that the best treatment plan for low-grade prostate cancer is “watchful waiting” to monitor its progression, instead of immediate surgery or radiation. Albertsen’s practice of active surveillance, and not intervention, for localized prostate cancer was reinforced by a recent long-term study published in September in the New England Journal of Medicine, on which Albertsen served as a consultant.

The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection.

Liver Disease

UConn Health is the first in Greater Hartford to use MRI to measure the stiffness of patients’ livers to reveal disease without the need for biopsy. Its MR elastography technique involves placing a paddle on a patient’s skin over the liver during MRI to create vibrations and measure the velocity of the radio waves penetrating the organ. This can indicate a stiffer liver and help diagnose fibrosis, cirrhosis, a fatty liver, or inflammation associated with hepatitis. The initiative is led by Dr. Marco Molina, radiologist in the Department of Diagnostic Imaging and Therapeutics.

“The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection,” Molina says. “Plus, with the obesity epidemic, patients developing nonalcoholic steatohepatitis (NASH), or fatty liver, can receive earlier diagnosis and take action to reverse their disease’s progression with diet and exercise.”

Breast Cancer

The new Women’s Center at UConn Health has opened its state-of-the-art Beekley Imaging Center, featuring advanced breast cancer screening. Dr. Alex Merkulov, associate professor of radiology and section head of women’s imaging, and his team are conducting research to test the effectiveness of using an abbreviated, five-minute MRI scan to confirm or rule out a breast cancer diagnosis. Typically, an MRI test takes 20 minutes, but researchers are seeing that a briefer MRI scan of just a few minutes can help provide a definitive answer to whether an abnormal breast growth is cancer or not — and potentially help women avoid the biopsy process.

Arthritis

The UConn Musculoskeletal Institute is now researching the use of MRI to assess and map the strength, weakness, and underlying makeup of a patient’s cartilage, especially for those with arthritis. The tool can allow orthopedic experts to identify any thinning or loss of cartilage in the body, which signifies moderate to late-stage disease. In early stages of arthritis, MRI can help pinpoint early morphological and subtle biochemical changes in cartilage.

Neurological Disorders

In neuroradiology, UConn Health is using the power of MRI to differentiate brain tumors, to detect strokes, to assess dementia, to diagnose multiple sclerosis, to evaluate traumatic brain injury, to find the source of epilepsy, and to guide brain surgery. In March 2017, leading neuroradiologist Dr. Leo Wolansky joins UConn Health to advance its research and chair the Department of Diagnostic Imaging and Therapeutics. Wolansky’s neuroimaging research has focused on enhancing understanding of MRI and its contrast agents, especially for multiple sclerosis and brain tumors. He also specializes in the hybrid imaging modality PET-MRI.

“Thanks to the power and advancement of MRI, doctors can see early evidence of disease and seize the opportunity to intervene and improve their patients’ health,” Molina says.