Next-Generation Sequencing Detects Rare Fusion Genes in Sarcoma Tumors

PHILADELPHIA (October 29, 2019) – Fox Chase Cancer Center researchers have determined that RNA-based next generation sequencing picks up gene fusions in sarcoma tumors that traditional gene testing may not. Sarcoma is a type of cancer in the bones and in connective tissue such as fat and muscle.

More than 80 percent of sarcoma types have two genes grouped together called fusion genes, said Shuanzeng Wei, MD, PhD, assistant professor in the Department of Pathology at Fox Chase. Different sarcomas can have specific fusion genes which can be used as diagnostic markers. Traditional tests such as fluorescence in situ hybridization (FISH), DNA-based next-generation sequencing, or polymerase chain reaction analysis may not catch all fusion genes in a tumor.

For example, FISH analysis may require running multiple tests to determine sarcoma type. But running one RNA sequencing analysis identifies all fusion genes in a sarcoma tumor, some of which may be unknown new fusion genes, said Wei.

“If we know exactly what type of sarcoma the patient has, we can then design a specific target treatment in a clinical trial instead of general chemotherapy or radiation,” Wei said of the study’s purpose.

The researchers obtained six sarcoma specimens from patients at Fox Chase who had previously been diagnosed with sarcoma using immunophenotyping or FISH analysis. The researchers then performed RNA sequencing and confirmed the gene fusions in five of the samples.

In the sixth sarcoma specimen, from a woman with a cervical spine tumor, the researchers discovered a rare fusion gene, EWSR1-PATZ1. Physicians at another institution had previously diagnosed the patient with low-grade spindle and small round cell neoplasm/sarcoma.

When Wei and his team performed a chromosome microarray analysis, they found no chromosome abnormality in the tumor. However, after RNA sequencing, they discovered the rare fusion gene and rediagnosed the patient with a low-grade glioneural tumor.

“RNA sequencing is not used for clinical purposes yet, but very soon it will be,” said Wei. “Hopefully, it will help accurately diagnose sarcoma and better manage the patients at our institution.”

The study, “Clinical Application of RNA Sequencing in Sarcoma Diagnosis: An Institutional Experience,” was published online in Medicine (Baltimore).

The study is collaboration between researchers from the Department of Pathology, the Genomics Facility, and the Cancer Biology Program at Fox Chase, as well as Temple University. The study is supported by an NCI grant P30 CA006927, a Comprehensive Cancer Center Core Grant.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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