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Research by Gibbs center director could affect colon cancer treatment

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An Upstate cancer researcher has identified a possible clinically-relevant benefit from tracking a gene that is considered the gatekeeper in development of colon cancer. Dr. Timothy J. Yeatman, president and director of the Spartanburg Regional Healthcare System’s Gibbs Cancer Center & Research Institute, said in a statement that the study he led “advances personalized or precision medicine for colon cancer.”

Yeatman and Dr. Michael J. Schell of Moffitt Cancer Center in Tampa, Fla., analyzed DNA sequencing from a large, human colon cancer database to identify the new treatment role from monitoring the Adenomatous Polyposis Coli gene, the Spartanburg Regional statement said. The APC gene is mutated in more than 70% of colon cancer cases.

The study published in the medical journal Nature Communications is titled A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC. Yeatman and other researchers plan to continue trying to “identify clinical uses for the sequencing of this gene and many others in the hopes of predicting drug responses and other applications, the statement said. Yeatman expects the APC gene sequencing discovery could impact decisions made regarding the proper treatment of patients with colon cancer,” the statement said.

Yeatman“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 an analysis of 1,321 cancer genes, the study results show 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,” the statement said.

According to the statement, precise 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, the statement said.

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, the statement said.

“No one has ever related these specific mutations to clinical outcomes — the chances that you’ll live or die,” Yeatman said.

Yeatman and others in the study used molecular and clinical databases originally developed as a collaboration between Merck and the Moffitt Cancer Center and more recently 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.

 

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