Genomics Screening

Illustration by Laura Wood


Clinical Genomics Screening Enables Targeted Cancer Therapy

By Lindy Keane Carter

Physicians treating patients with cancer now have a resource at MUSC Health that can help them predict which patients may have a therapeutic response to a specific drug. The 2014 acquisition of the MiSeq™ desktop sequencer (Illumina; San Diego, CA) enabled the Clinical Genomics Laboratory at MUSC Health to offer state-of-the-art next-generation sequencing to its cancer patients. This screening service was described in a feature article in the Summer 2014 Progressnotes. Now, the laboratory is extending that service to cancer patients with certain solid tumors throughout South Carolina. The MiSeq™ analyzes tumor samples against a panel of 26 cancer-related genes to identify variants for which targeted therapies have been developed or are being evaluated in clinical trials. Molecular information will play an increasingly important role in clinical diagnosis and management of patients with cancer. For example, an international working group of neuropathologists recently recommended guidelines on how this information will be incorporated into the next World Health Organization classification of central nervous system tumors.

“We are pleased to offer this important testing to patients beyond our clinics so that all patients in South Carolina can benefit from precision medicine initiatives,” says Daynna J. Wolff, Ph.D., Professor in the Department of Pathology and Laboratory Medicine and Director of Cytogenetics and Molecular Genetics and Genomics.

Targeted cancer therapy blocks the growth and spread of cancer by disrupting the signaling pathways that promote tumor growth. In contrast, most standard chemotherapies act on all rapidly dividing cells, normal and cancerous. Because targeted therapy is directed at the tumor growth process, it does not affect the healthy surrounding cells. Thus, the new approach to fighting cancer is to focus on the gene mutation that gives rise to the tumor, not the type or location of the tumor. As an example, 40 percent to 60 percent of melanoma patients with a certain mutation will respond to a known therapeutic drug.

The cancers that can be screened are colorectal cancer, non-small cell lung cancer, melanoma, and any metastatic tumor, regardless of origin. The 26 genes in the cancer panel are: AKT, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, SRC, STK11, TP53.

The laboratory is currently revising this panel to include the IDH1 and IDH2 genes so that the test can also help to guide therapy for glioblastoma brain tumors. Additional genes will be added as new therapies are introduced. Julie Woolworth Hirschhorn, Ph.D. Associate Director of the Genomics Laboratory, reviews current literature and communicates frequently with MUSC Health’s clinicians to stay up to date on new gene targets or therapies. The laboratory staff then integrates this information into the gene-sequencing panel.

The ordering physician will receive a report that indicates the gene variants that are present, the mutations known to respond favorably to targeted therapy, and resistant mutations known to negate the therapeutic response to targeted therapies. Potential clinical trials also can be shared with the physician upon request.

“We tend to see a dramatic effect with these targeted therapies because you’re targeting more of the drug to the tumor and because, when the pathways are inhibited, the tumor growth slows or stops,” says Wolff.

For more information or specific instructions on using the services of the Clinical Genomics Laboratory, physicians may contact MUSC Health Laboratory Client Services at 843-792-0707. The ordering physician will receive a report within 7 to 12 business days.