Telomere Biology

N.W. Kim, M.A. Piatyszek, K.R. Prowse, C.B. Harley, M.D. West, P.L.C. Ho, G.M. Coviello, W.E. Wright, S.L. Weinrich, J.W. Shay, "Specific association of human telomerase activity with immortal cells and cancer," Science, 266:2011-5, 1994. (Cited in nearly 80 publications through April 1996) Comments by Jerry Shay, University of Texas Southwestern Medical Center, Dallas END RUN: Texas' Jerry Shay, left and Woody Wright developed a telomerase activity assay. Although telomeres-the tips of chromosomes-have been studied since the early part of this century, it wasn't until a few years ago that the field really took off (R. Lewis, The Scientist, Feb. 19, 1996, page 12). This paper, published in December 1994, describes a polymerase chain reaction (PCR)-based assay for measuring the activity of telomerase, the enzyme that controls telomere length. But more important, according to Jerry Shay, a professor of cell biology and neuroscience at the University of Texas Southwestern Medical Center in Dallas, is that the test showed telomerase was active in 90 percent of the cancer cell types screened. Shay calls telomere biology "one of the two or three most exciting areas in cancer research today." He adds that "what also makes this a particularly interesting project is that it's a great example of academic and industry labs working together to solve a problem." Researchers at the medical center worked closely with scientists at Geron Corp. in Menlo Park, Calif. ASSAYERS: From left, researchers Nam Kim, Scott Weinrich, and Mieczyslaw Piatyszek "My close colleague, Woody Wright [a professor of cell biology and neuroscience, also at Texas], came up with the idea for the assay. We played around with it to make it a PCR-based test. The first author, Nam Kim, now a senior scientist at Geron, and Scott Weinrich, also a senior scientist at Geron, essentially took our preliminary data and figured out how to make it really work. After Scott and Nam got the assay working, Geron gave us the details. Then Mieczyslaw Piatyszek, a postdoc in my lab, ran through over 100 tumor types to see if the assay would work or not." Shay also notes the practical importance of the assay: "People have no problem picking up this technique." He says a research test kit for measuring telomerase activity was released in early May and the test distributor, Oncor Inc., based in Gaithersburg, Md., has already received more than 500 requests for it. Most of the requests have come from molecular pathologists, who plan to use the kit to assay their tissue collections for telomerase activity. He cites two areas in oncology in which the assay might be most useful. "In some instances, telomerase is detected early in the progression to cancer, so the enzyme could turn out to be a unique or early marker of cancer. That's desperately needed, especially in colorectal and breast cancers." The second use of the test is what Shay terms a "prognostic indicator of outcome." He says that in at least three cancer types, "high telomerse activity equals poor prognosis [E. Hiyama et al., Nature Medicine, 1:249-55, 1995; E. Hiyama, Cancer Research, 55:3258-62, 1995; W. Zhang et al., Clinical Cancer Research, 2:799-803, 1996]. This could be very useful, albeit not very reassuring, information." Shay observes that there are probably two reasons that his and other telomere papers are being cited so often by colleagues. The first is related to the subject's relationship to the burgeoning field of molecular biology and genetics of aging. The other is related to applications of telomere biology to other areas of molecular biology. "We're still at the early stages, where all the fine points are starting to be hashed out," he explains. "Are there cell cycle aspects? What are the genes that regulate telomerase activity? Are therapies that inhibit telomerase activity going to be important in cancer treatment?" He says that the telomerase assay has made experiments to address these questions more "practical," whereas "a few years ago this was difficult and required large amounts of tissue." Shay and colleagues are now studying the relationship between telomere genetics and tumor suppressor genes (W.E. Wright, EMBO Journal, 15:1734-41, 1996; H. Ohmura et al., Japanese Journal of Cancer Research, 86:899-904, 1995) and why there are different rates of telomere shortening in different cell types, an area with implications for AIDS research.

Telomere Biology

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