genetics

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.

UConn to Establish Genetic Counseling Master’s Program

illustration of genetic material


UConn has awarded $300,174 to seed a new Professional Science Master’s (PSM) Program in Genetics, Genomics, and Counseling. Graduates of the program will work with doctors and patients to interpret the results of genetic testing, a rapidly growing area in health care that needs more trained personnel. Once accredited, the program will be the first in Connecticut and the only one in New England at a public institution.

“Our students are anxious. They want to do this,” says Judy Brown, director of the diagnostic genetic sciences program in UConn’s College of Agriculture, Health, and Natural Resources’ allied health sciences department. Brown is spearheading the push for the program along with Institute for Systems Genomics director Marc Lalande and UConn Health genetics counselor Ginger Nichols.

Once accredited, the program will be the first in Connecticut and the only one in New England at a public institution.

New genetics research and techniques have made it easy for the average person to get a read on their genome, or whole genetic code. Celebrities, including Angelina Jolie, who have openly discussed their genetic risk factors for cancer, and companies, such as 23andMe, that will provide a basic genetic report for a fee, have increased demand enormously. But there’s a lack of trained people who can accurately interpret and explain the results of genetic tests, limiting the potential benefits.

Ideally, a doctor who identifies “red flags” within a patient’s family history that indicate increased genetic risk for disease will call in a genetic counselor. The counselor can take a detailed family history, determine the appropriateness of genetic testing, discuss benefits and limitations of testing to help the patient make an informed decision, and advise the patient on who else in their family might be at risk. If testing occurs and results indicate high genetic risk, counselors can help discuss the options to mitigate that risk.

As a result, genetic counseling is the fourth-fastest-growing occupation in Connecticut. Many UConn allied health sciences majors would like to enter the profession, Brown says, but there are only 34 training programs in the U.S., and the acceptance rate is below 8 percent.

Institutions including Connecticut Children’s Medical Center and The Jackson Laboratory (JAX) have expressed support for the program. Kate Reed, director of the Clinical and Continuing Education Program at JAX, says JAX would combine its experience translating genetic discoveries into clinical applications with UConn’s experience in this area to give the PSM graduates a solid understanding of the research behind clinical treatments.

The exact roles of JAX, Connecticut Children’s, and the other institutions who support the new PSM have not yet been defined. The program’s curriculum first needs to be approved and accredited. The first students are expected to start the program in fall 2018.

Lab Notes – Winter 2015

Cancer Cells Unreceptive to Vitamin D

Many human colon cancers may not express receptors for vitamin D, limiting vitamin D’s protective role against colon cancer to the early stages of the disease, report Charles Giardina and colleagues at UConn’s Department of Molecular and Cell Biology and Center for Molecular Medicine in the April 14 issue of Cancer Prevention Research. The researchers observed that adenomas in the colons of mice tended to repress vitamin D receptors, while having elevated Class I histone deacetylases (HDAC). However, HDAC inhibitors may reactivate the vitamin D receptors. They propose that vitamin D could still be protective against colon cancer, but how its receptors are expressed and inhibited in cancer cells needs more examination. Read the article at Cancer Prevention Research.

a group of vitamin D suppliments


Rogue X Chromosomes Uncovered in Farmington

Humans only need the genes from one X chromosome to be healthy. The extra one gets trussed up and shut down in the earliest stages of development. But female human embryonic stem cells growing in the lab sometimes reactivate their second X. They express extra genes, fouling up experiments and scuttling potential therapies. Now, researchers including UConn’s Marc Lalande and a team from Paris Diderot University have found a marker, and potentially a mechanism, for how the extra X reactivates – and they have an idea on how to prevent it. They describe their findings in the May 7 issue of Cell Stem Cell.


Friends are Unreliable Sources for Drinking Studies

In recent years, researchers have turned to friends of people in alcohol studies to verify what the subjects report about their drinking habits. People in the same social situations are sought out, in part, because of the inherent impairment caused by alcohol. But according to a UConn study published in Addictive Behaviors, friends don’t seem to provide any new information. In fact, they typically underreport what their acquaintances consume. The finding supports the so-called “protective effect” of friends described in other research. A growing availability of other evidence – hair and fingernail samples, for example – may provide better strategy for corroborating the amount of alcohol study subjects consume, says author Michael Fendrich, associate dean of the School of Social Work.


She Smells Him, She Smells Him Not

Mice rely on their noses to help them navigate the world. But high levels of progesterone “blind” receptors in the noses of female mice to male pheromones, UConn Health’s John Peluso and other colleagues, led by Dr. Lisa Stowers of The Scripps Research Institute, report in the June 4 issue of Cell. Female mice have high levels of progesterone during the infertile phase of their reproductive cycles, and tend to be indifferent or even aggressive toward males. But during the fertile phase, progesterone levels drop and estrogen rises, and their nasal receptors again respond to male pheromones, the researchers found. Female mice in their fertile phase are friendly and sexually receptive towards males – perhaps because they can smell them.

mouse