Study undertaken at Gibbs Cancer Center & Research Institute
The study, published in prestigious medical scientific journal Nature Communications in June 2016, entitled “A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC,” focuses on the Adenomatous Polyposis Coli (APC), a gene that has long been considered the “gatekeeper” in the development of colon cancer.
Yeatman, lead investigator at the Gibbs Cancer Center & Research Institute, along with Dr. Michael J. Schell of Moffitt Cancer Center in Tampa, Fla., performed extensive analysis of DNA sequencing from a large, human colon cancer database to identify a new, clinically-relevant role for APC, that is mutated in more than 70 percent of colon cancer cases.
“The fact that APC mutation is so common would suggest that it wouldn’t have any other role than simply to initiate colon cancer,” Yeatman said. “But we found this not to be the case.”
Starting with analyzing 1,321 cancer genes, the study results found that gene sequencing of APC and other associated genes reveals a prognostic effect that could help physicians better predict long term outcomes. Previously, APC had not been commonly sequenced in many clinical panels.
“This advances personalized or precision medicine for colon cancer,” Yeatman said.
Precision medicine promotes personalized medical care, with decisions, practices, and/or products tailored to each patient, often based on genetic testing. Precision medicine considers “individual variability in genes, environment and lifestyle for each person,” according to the National Institutes of Health.
The precision of gene sequencing is key. A cancerous colon tumor may be caused by a number of mutations. All genes have two copies, one from the mother and one from the father. These pairs are classified by four variations: (1) wild type (normal), with no associated mutations in either copy; (2) one mutation present, one copy missing; (3) one mutation present, one normal copy present; or (4) both copies mutated.
As common as APC mutation is in colon cancer, tumors with normal APC genes produce some of the worst outcomes, along with tumors containing two mutations, according to study results.
Also in play for prognostic differences are the locations of mutations within the gene, types and numbers of mutations associated with each tumor, and mutations in genes with which APC partners.
“No one has ever related these specific mutations to clinical outcomes — the chances that you’ll live or die,” Yeatman said.
The results that Yeatman and colleagues discovered were possible because of the ability to sequence a lot of tumors. In fact, one of the world’s largest molecular and clinical databases on colon cancer is the basis for the research. The database was originally created as a collaboration between Merck and the Moffitt Cancer Center and more recently, a collaboration with the Gibbs Center & Research Institute.
“That’s why it’s so important for patients to participate in research and for institutions to collaborate,” Yeatman said.
Yeatman, a surgeon who specializes in surgical oncology, liver cancer and colorectal cancer, performs research at the state-of-the-art, 10,000-square-foot lab at Gibbs Cancer Center & Research Institute, which oversees as many as six research projects at any given time.
Because Gibbs is the next generation “hybrid academic/community” cancer center, its focus is on translational research and clinical care, also known as “lab bench to patient bedside.” This approach promises to bring discoveries from the lab to the patient in a much faster time frame, according to Yeatman. The gene sequencing highlighted in the article has already been taking place at Gibbs for a year.
“I suspect that more clinicians will start looking at this gene, and consider including it in their sequencing panels,” said Yeatman, who has spent a lifetime researching colon cancer and has published papers in Science, Nature Medicine, Nature Genetics, and Nature Cancer Review, among others. His research has been federally funded without interruption since 1994. This study was funded by a grant from the National Cancer Institute.
The next step: Yeatman and other researchers will continue to try to identify clinical uses for the sequencing of this gene, and many others in the hopes of predicting drug responses and other applications. At some point, Yeatman suspects that the APC gene sequencing discovery could impact decisions made regarding the proper treatment of patients with colon cancer.
About Gibbs Cancer Center & Research Institute
Gibbs Cancer Center & Research Institute is a nationally recognized cancer treatment and research facility associated with the National Cancer Institute Community Cancer Center program and the Medical University of South Carolina. Named for benefactors Marsha and Jimmy Gibbs and with locations in Spartanburg, Gaffney and Greer, Gibbs is a proven leader in providing effective cancer treatment through advanced technology, professional expertise and an exceptional level of personalized care. Gibbs’ oncology program, which also includes the Bearden-Josey Center for Breast Health, has been recognized by the Commission on Cancer of the American College of Surgeons as offering high-quality cancer care. In 2012, Gibbs joined forces with Bon Secours St. Francis Health System to expand world-class oncology services and clinical research in the Upstate. In 2013, the Gibbs expanded its research efforts by opening a 7,500-square-foot state-of-the-art facility at Pelham Medical Center. In May 2016, Gibbs broke ground on a new 198,000-square-foot facility in Greer, S.C. on the existing Pelham Medical Center campus, and is scheduled for completion in mid-2018. The seven-story building will be home to multidisciplinary experts from numerous specialties who will discuss each patient’s healthcare plan and treatment options, including access to cutting-edge clinical research.
About Spartanburg Regional Healthcare System
Spartanburg Regional Healthcare System (SRHS) offers a full spectrum of services through four hospitals: Spartanburg Medical Center, Pelham Medical Center, Spartanburg Hospital for Restorative Care and Union Medical Center. SRHS also includes Ellen Sagar Nursing Center,
113-bed long-term care, skilled nursing facility that offers nursing care and rehabilitation services. SRHS provides unparalleled oncological care through the Gibbs Cancer Center & Research Institute. The multidisciplinary Medical Group of the Carolinas has more than 350 physicians across seven counties in two states. SRHS employs nearly 6,000 associates and offers outpatient surgery centers, a vibrant post-acute division, and a Level I Trauma Center. U.S. News and World Report ranked Spartanburg Medical Center the No. 1 regional hospital in South Carolina in 2014-15. The Commission on Cancer gave Gibbs Cancer Center & Research Institute its Outstanding Achievement Award.