“First of all, SDH5 has a new name,” says Joshua Schiffman, MD, a pediatric oncologist, assistant professor in the Department of Pediatrics, and an HCI investigator. “It’s now known as SDHAF2, which stands for SDH Assembly Factor 2.” The Human Genome Organisation, which approves names and symbols for each known human gene, gave it the new name. The designation provides an international standard for referring to this gene.

“The 2009 research in which I participated found mutations in SDHAF2 in a Dutch family with inherited paragangliomas [a type of head and neck cancer],” says Schiffman. “We have not found any SDHAF2 mutations among our HCI patients, but we offer SDHAF2 testing to members of families with multiple paragangliomas whose genetic tests show they do not have any of the three other known SDH gene mutations.”


                                                    Joshua Schiffman, MD

One of the rules of science is that other researchers must be able to reproduce results. Jared Rutter, PhD, associate professor of biochemistry at the University of Utah School of Medicine and a member of HCI’s Nuclear Control of Cell Growth and Differentiation Program, led the team of researchers who originally discovered SDHAF2’s connection to paraganglioma. “During 2010, other labs worldwide have found SDHAF2 mutations in paraganglioma,” he says. “The gene mutation has also been found in pheochromocytoma [a cancer of the adrenal glands]. These are significant advances because they increase the effectiveness of genetic screening in other tumor types. It is likely that SDHAF2 mutations will also be found in other types of cancer, and we are actively pursuing this question.”


                                                      Jared Rutter, PhD

“We’re also continuing work on other genes that might have functions similar to SDHAF2 to see if they are mutated in paraganglioma and other cancers,” says Rutter.

Three labs certified under the Clinical Laboratory Improvement Amendments (CLIA) now offer the SDHAF2 test in their panels of genetic tests, moving it beyond research and into public access. CLIA, under the U.S. Food and Drug Administration’s mandate, establishes quality standards for all laboratory testing to ensure the accuracy, reliability, and timeliness of patient test results regardless of where the test was performed. 

Schiffman adds, “In our research lab, I’m working with HCI’s head and neck surgeons to obtain samples of paraganglioma tumors to create cell lines that will allow more testing of how these cancers develop.

“It brings HCI’s fantastic model of translational research full circle. We started from the basic science of metabolism and identifying new genes related to paraganglioma and used the discoveries to develop screening for patients at high risk of carrying SDH mutations. This in turn has allowed early cancer detection in patients before they even know they have a tumor and then using cells from the removed tumors to learn more about the cancer and develop new preventive and therapeutic strategies.”

Read the 2009 Annual Report story From Lab Discovery to Life-Saving Paraganglioma Screenings in Six Months.