Cancer Genetics

C.J. Hussussian, J.P. Struewing, A.M. Goldstein, P.A.T. Higgins, D.S. Ally, M.D. Sheahan, W.H. Clark, M.A. Tucker, D.C. Dracopoli, "Germline p16 mutations in familial melanoma," Nature Genetics, 8:15-21, 1994. (Cited in nearly 130 publications as of February 1996) Comments by Christopher J. Hussussian, Washington University School of Medicine This paper identifies and describes mutations in the p16 gene in families with malignant melanoma. These mutations affect the balance between the proteins p16 and cyclin D, which play a role in controlling the cell cycle. When the biochemical balance between these two regulators goes awry, abnormal cell growth can result. NOT JUST SKIN DEEP: Washington University researcher Christoper J. Hussussian and NIH coworkers identified in the p16 gene in families with a hitory of malnigant melanoma. "Although 2.5 percent of all cancers are melanomas, its incidence is doubling every 10 to 20 years," notes Christopher J. Hussussian, a sixth-year surgical resident at the Washington University School of Medicine. "Next to lung cancer in women, it's the fastest-growing form of cancer in terms of prevalence in America." The research group found eight mutations in the 18 families they studied. Hussussian performed this research at the National Institutes of Health's National Center for Human Genome Research as part of his general surgery training program at Washington University. He collaborated with Jeffrey Struewing, a genetic epidemiologist, and others at the National Cancer Institute. The "widespread interest" in his paper, comments Hussussian, is likely due to another p16 paper published earlier in 1994 by Alexander Kamb from Myriad Genetics Inc. in Salt Lake City (A. Kamb et al., Science, 264:436-40; cited in more than 450 publications as of February 1996). This article suggests p16's role as the initiator of many types of cancers, in addition to melanoma. "People thought p16 was the next p53 [another cell cycle-regulator gene implicated in many cancers]," recalls Hussussian. However, after the 1994 Science article by Kamb, "there was a flurry of papers where mutations of p16 were not found. There was somewhat of a backlash, and people started to doubt whether or not it was an important gene in any cancer. "Our paper was really the first to show-after the original paper-that indeed there seemed to be a role for p16 in at least the development of melanoma. People had suspected there was a gene for melanoma on chromosome 9 for a long time, but no one really knew which gene it was." Kamb's group also published an article on p16 in the same issue of Nature Genetics as Hussussian's paper (A. Kamb et al., Nature Genetics, 8:22-6, 1994; cited in 85 publications as of February 1996). "But they screened and found a low rate of mutations," says Hussussian. "It turns out from subsequent data that they missed mutations in some families; they've recently found mutations in them. It's kind of ironic because they were the first ones to describe and ignite interest in the gene." As an update, Hussussian mentions that "there's been a couple of other papers published that corroborate our findings": G.J. Walker et al., Human Molecular Genetics, 4:1845-52, 1995; and N.A. Gruis, Nature Genetics, 10:351-3, 1995. The latter paper describes the recently found mutations in the families studied by Kamb. The articles listed here, all less than two years old, have received a substantially greater number of citations than others of the same type and vintage, according to data from the Science Citation Index¨ of the Institute for Scientific Information, Philadelphia. Why have these research reports become such standouts? In conversations with The Scientist, the authors attempt to provide an answer.

Cancer Genetics

Interested in reading more?

Become a Member of