Hopkins researchers have discovered that male hormones seem to be behind a bad marriage of two genes that’s found in nearly half of all prostate cancers. The finding, published in Nature Genetics, adds another brushstroke to a complicated picture, and may lead to new strategies to help prevent prostate cancer.
Cancer happens when something goes wrong in our genes; these mutations are called “acquired defects.” In this case, a gene named TMPRSS2, which is controlled by male hormones, called androgens, breaks off from its original site in the cell nucleus and fuses with another gene, called ERG. The result is that prostate cancer cells respond to androgens by speeding up their growth. In previous research, led by Vasan Yegnasubramanian, M.D., Ph.D., with William G. Nelson, M.D., Ph.D., Michael Haffner, M.D., and others, Hopkins scientists found that androgens use an “untangling enzyme” to splice these genes.
“These types of defective fusions,” says Nelson, “have long been thought to be caused by errors in copying the genome when cells divide, or by mistakes in fixing the genome when it is damaged by cancercausing chemicals, such as those found in foods or other environmental factors that are linked to cancer.” These new findings, he adds, “hint that the origin of the fusion events — which are so common in prostate cancer — may be the accidental breaking of TMPRSS2 upon activation by male hormones.”