July 20, 2016

Breast cancer: finding the smoking gun

A new method developed at Vanderbilt may help “inventory” all tumor-promoting genes.

Many genes are associated with cancer. The trick is proving they actually promote tumor formation.

One approach, detailed by Ian Macara, Ph.D., and colleagues last month in Cell Reports, is an in vivo “gain-of-function” screen.

The researchers used a gene “library” (complementary DNA carried by lentivirus) to increase the expression of nearly 1000 different genes in mouse mammary glands, and asked if any of these genes would accelerate the formation of mammary tumors.

Five genes that promoted tumor formation were identified, four of which were not previously known to be breast cancer genes.

Expression of one of these genes, GTF2IRD1, is known to be significantly increased in human breast, lung and ovarian cancers and is correlated with poor overall survival. The current study suggests that “GTF2IRD1 is a bona fide tumor-promoting gene relevant to human cancer,” the researchers concluded.

A genome-wide application of this approach may help achieve the first complete inventory of tumor-promoting genes, and thus fulfill the promise of precision cancer medicine, they added.

This study was supported by research grants from the National Institutes of Health (CA132898, CA197571, CA100374) and by a Department of Defense postdoctoral fellowship (W81XWH-11-1-0083).

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