Genetics, Genomics and Gene Sequencing Sarcoma at Sylvester
Article Summary
- Sylvester Comprehensive Cancer Center researchers are using a variety of tools centered on molecular genetics to better understand sarcoma.
- Sylvester’s Genetic Predisposition Syndrome Clinic tests people who have a genetic predisposition for sarcoma.
- Pathology and gene sequencing plays an important role at Sylvester in choosing, implementing and monitoring a treatment plan.
Sarcoma is a rare cancer type that most commonly develops in the bones and soft tissues. According to the National Foundation for Cancer Research, 17,560 people will be diagnosed with sarcoma each year. About 900 of those patients will be treated at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
Sylvester is at the forefront of sarcoma diagnosis, treatment and research. Collaborations between clinicians, researchers and basic scientists using a variety of tools centered on molecular genetics to better understand the disease in general, as well as the variability in biological behavior between individual patients.
“It’s really an incredibly exciting time at Sylvester, as far as sarcoma diagnosis, treatment and research,” said David Lombard, M.D., Ph.D., co-leader of the Cancer Epigenetics Program at Sylvester and professor of pathology and laboratory medicine.
Genes Help Stratify Sarcoma Risk
“Genetic testing is important in many types of cancer, including sarcoma, because there is a hereditary predisposition to some cancer types,” said Jonathan Trent, M.D., Ph.D., director of the sarcoma oncology group at Sylvester and professor in the Division of Medical Oncology at the Miller School.
There are hereditary syndromes that increase an individual’s risk of a variety of cancers, including sarcoma. One example is Li-Fraumeni syndrome, which is caused by a mutation in the gene TP53, leading it to produce a damaged p53 protein.
P53 regulates the division and proliferation of cells and suppresses tumors by preventing cells from dividing in an uncontrolled manner. A mutated TP53 gene predisposes people to a variety of cancers, including sarcomas, leukemias, breast cancer, brain tumors and others.
“If we see a 25-year-old who is found to have a sarcoma that’s hereditary in nature and their 27-year-old sibling also has the mutation, we start screening them [for cancers] immediately, really,” said Dr. Trent.
The Genetic Predisposition Syndrome Clinic at Sylvester is crucial because “this is an emerging area of medical insight, with important benefits for patients and their families, and we’re just scratching the surface at this point,” added Dr. Lombard.
Rare Cancer, Rare Tissue Samples
Sylvester’s patients are invited to share their tissue samples with the sarcoma tissue bank and registry.
“All translational research starts with patient tissue,” said Dr. Lombard.
Because the disease is rare, and Sylvester has “a strong multidisciplinary group in treating patients with sarcoma, we attract a lot of patients with the disease, which gives us a portal in obtaining a large number of sarcomas specimens,” said Andrew Rosenberg, M.D., a Sylvester researcher and professor of pathology and laboratory medicine at the Miller School.
Dr. Lombard added, “This is really a unique opportunity for us to assemble tissues, as well as bank other material from these patients, such as serum, to provide the foundation for our work to develop the next generation of cures.”
Much of Dr. Rosenberg’s work focuses on improving sarcoma diagnosis. He studies unusual sarcomas by “correlating their microscopic features with their molecular genetics and biological behavior,” he said.
Doing so not only helps researchers understand sarcoma, but a variety of other cancers as well.
Dr. Lombard and his team are working on targeting a gene called SIRT5 in sarcoma using metabolomics, which analyzes molecules that the body produces during metabolism to better understand how the tumor is interacting with the patient. Better known for its role in aging, recent research has found that the SIRT5 gene plays an important part in cancer biology.
“When we eliminate SIRT5 from certain types of cancer cells, including specific sarcomas, those cells die,” said Dr. Lombard, making it an attractive drug target. Plus, “the really exciting thing about SIRT5 is that when we delete this gene [in preclinical trials] or from normal cells, they remain pretty healthy.”
That discovery suggests a drug targeting SIRT5 may kill cancer cells with limited side effects for the patient.
Right Patient, Right Treatment
Once a person is diagnosed with sarcoma, pathology and gene sequencing plays an important role in choosing, implementing and monitoring a treatment plan. In fact, Dr. Rosenberg often examines tissue samples from a patient who is still undergoing surgery in real time, so he can provide advice to guide the surgeon through the remainder of the procedure.
Scientists will sequence both the tumor and the circulating blood for genetic mutations and metabolites that tell clinicians which drugs might be most effective for which patients.
“Precision medicine approaches are common in sarcoma, so we rely heavily on testing the tumor, testing the blood in those situations,” said Dr. Trent. “Anybody with a diagnosis of a rare disease, such as sarcoma, should at least have an initial evaluation at an experienced, high-volume center of excellence such as Sylvester.”
Tags: cancer research, Dr. Andrew Rosenberg, Dr. David Lombard, Dr. Jonathan Trent, Gene sequencing, genetics, genomics, sarcoma, Sylvester Comprehensive Cancer Center