An Interview with Bert Vogelstein and Kenneth Kinzler
2014; American Association for Clinical Chemistry; Volume: 61; Issue: 1 Linguagem: Inglês
10.1373/clinchem.2014.223271
ISSN1530-8561
Autores Tópico(s)Cancer-related Molecular Pathways
ResumoBert Vogelstein was a young assistant professor in 1983 when Kenneth Kinzler came to interview for a position as a graduate student. Wearing a powder blue suit, and sporting a deep Philadelphian accent, Kinzler was hired on the spot. It was an exciting moment. Vogelstein had just embarked on what would become a career-defining approach to cancer—looking for genetic mutations in human tumors, specifically colorectal tumors. Over the next five years, working with Kinzler and other members of his lab at Johns Hopkins, Vogelstein would discover that colorectal cancers arise as the result of a stunningly specific sequence of genetic alterations. They published their results in 1988 in the New England Journal of Medicine . The following year, they showed that the crowning mutation in the sequence occurred in the then-obscure p53 gene. Discovered ten years earlier, p53 [ TP53 (tumor protein 53)1] was thought to be an oncogene, inspiring cancers when intact and overexpressed, not when mutated or missing. Vogelstein and his colleagues showed that in its healthy state, the p53 protein is a tumor suppressor—the first ever found. They would go on to show that p53 mutants are found in a broad array of cancers. A rush of papers elucidating the role of p53 , along with other tumor suppressors such as adenomatous polyposis coli ( APC ), flowed from the lab. Between 1990 and 1996, Vogelstein was the most cited biomedical scientist in the world, followed immediately by Kinzler. In the early 2000s, overcoming considerable technical and intellectual hurdles, they moved from pinpointing individual mutations to mapping the entire genome of cancer cells. They have been celebrated with accolades and awards—Vogelstein was among the first recipients of the Breakthrough Prize in the Life Sciences, which carries three million dollars—yet the two men appear almost oblivious to the …
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