Prize-Winning Genetics Research Yields Test for Prostate Cancer

Early-career coup. Identifying a marker for prostate cancer earned Scott Tomlins 
(left, with AAAS CEO Alan I. Leshner) a major AAAS award. [AAAS/Carla Schaffer]

One out of every six men in the United States will be diagnosed with prostate cancer in his lifetime. Many of these cases are detected with the so-called PSA blood test, but this test is prone to false positives and may be followed up with a more invasive biopsy.

Another option should soon be available in the form of a urine test, which could complement the PSA as a way to identify men at highest risk for prostate cancer. The test is based on the discovery by Scott Tomlins of the University of Michigan Medical School that two particular genes are fused together in almost half of all prostate cancers and are thus a useful marker for the disease.

The test is expected to be available within the year through the University of Michigan's CLIA-certified Michigan Center for Translational Pathology, according to Tomlins. Although the test is not yet approved by the Food and Drug Administration, the federal Clinical Laboratory Improvement Amendment, or CLIA, allows individual laboratories to offer diagnostic tests to patients, without FDA approval.

The discovery of this gene fusion is notable not only for its scientific and clinical implications but also because the researcher behind it is just 34 years old. AAAS and the journal Science Translational Medicine on 15 July honored Tomlins' work with the inaugural AAAS Martin and Rose Wachtel Cancer Research Award. This $25,000 prize recognizes outstanding work by young scientists performing breakthrough cancer research.

Tomlins' discovery "altered the way the field thought about the genetic causes of the common solid tumors — not only prostate but also lung, breast, and colon cancer," said Katrina Kelner, a member of the award selection committee and Editor of Science Translational Medicine.

When Tomlins began doing research at the University of Michigan, where he earned his M.D. and Ph.D. degrees, he was more interested in using DNA microarrays as a tool to study cancer generally. Lured by a free lunch, Tomlins attended a seminar by Arul Chinnaiyan, a University of Michigan scientist who had just published one of the first studies using microarrays to study prostate cancer. Chinnaiyan eventually became Tomlins' scientific mentor.

"Although I sort of landed in prostate cancer by chance, it's an enormous public health problem, and there are so many nuances to both the clinical management and molecular alterations that it's still incredibly interesting to work on," Tomlins said.

Prostate cancer is a leading cause of cancer death in American men, second only to lung cancer. Although the disease can be fatal, success stories are common, and many patients are cured by surgery or radiation. Tomlins and his colleagues found that two genes named TMPRSS2 and ERG are incorrectly glued together in almost half of all prostate cancers. In normal prostate cells, ERG is turned off and TMPRSS2 is turned on.

When parts of TMPRSS2 in the prostate become fused to ERG, ERG is turned on. Once activated, ERG drives cancer development by inappropriately turning on or off other genes. This gene fusion is the most specific marker of prostate cancer yet to be found.

Tomlins' work on gene fusions spurred the development of the new test for prostate cancer, first published in the 3 August 2011 issue of Science Translational Medicine, which can detect the product of the gene fusion in patients' urine.

More recently, he and his colleagues have been working on another test, which combines the urine-based detection of gene fusions with the detection of elevated serum PSA levels.