Vanderbilt Researchers Find Potent Genetic Risk Factor for Breast Cancer

Researchers at Vanderbilt University have found a powerful new genetic risk factor for breast cancer.

Using data from population-based studies of women in Shanghai, China, Jirong Long, Ph.D., assistant professor of Medicine, and colleagues discovered a deletion in a cluster of genes, called APOBEC3 genes, that are known to trigger DNA mutation and which have previously been implicated in cancer.

If a woman has a deletion in one of the two sets of genes she inherits from her parents, her risk of breast cancer increases by 31 percent. If the deletion is present in both sets of genes, her risk increases by 76 percent.

“This is the first copy number variation or CNV identified for breast cancer and is one of the strongest common genetic risk variants identified so far for breast cancer,” the researchers reported in the Journal of the National Cancer Institute.

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Guest Blog Post – The Biologic Picture of Melanoma

Jeffrey A. Sosman, M.D., Director, Melanoma and Tumor Immunotherapy Program
Vanderbilt-Ingram Cancer Center

In the past 10 years, mutations found in melanoma (the most deadly form of skin cancer) have led directly to the development of effective therapies. One example is the BRAF mutation and its inhibitor drug vemurafenib.

The New York Times reported on a new finding uncovered in the DNA of a large number of melanomas tested with extensive DNA sequencing of the whole genome.  This new mutation found by two independent groups is actually not present in a gene that produces a functional protein or enzyme.  Instead, it is a mutation in the portion of the DNA that regulates the expression of an enzyme, telomerase. Telomerase protects the chromosomes from breakdown and the cell from death. High levels of telomerase are seen in many cancer cells, including melanoma, and it protects the cancer cells from a normal dying process.

In a mechanism previously never reported, the newly discovered mutation changes the regulatory portion of DNA so it may be very vulnerable towards activation. In this way, the mutation indirectly allows the telomerase level to increase.

This mutation is found in these exact locations in about 70 percent of melanomas. The mutation provides a link between the BRAF mutations and the regulatory portion of another gene.

The new discovery adds one more piece to the biologic puzzle of melanoma. With each additional piece we are closer to completing the biologic picture of melanoma, which will further our ability to define treatment approaches to kill this deadly cancer.