Two University of Utah researchers intrigued nearly 10 years ago by a single family with a rare hereditary form of eye cancer - will this week receive one of the nation's top honors for "one of the most important discoveries in human cancer genetics."
Drs. Raymond L. White and Webster K. Cavenee will be awarded the Charles S. Mott Prize, sponsored by the General Motors Cancer Research Foundation, for providing the first genetic proof that loss of a protective suppressor gene can trigger cancer.Their joint studies, and recent investigations conducted independently, are leading to development of tests that can indicate inherited predisposition to certain cancers. Their work also lays a foundation that may help scientists predict the likelihood of disease and then prevent it by treating cells with the precise protein they are missing.
The researchers' work all started in the early 1980's.
"We heard about an unusual family with retinoblastoma (eye cancer), and the pattern of inheritance was intriguing," said White, co-chairman of the U.'s Department of Human Genetics and investigator, Howard Hughes Medical Institute. "It fit with something we were working on, sparked us, got us over the energy barrier."
Cavenee, who's now director of the Institute for Cancer Research, Montreal Branch of the Ludwig Institute for Cancer Research and McGill University, was a National Cancer Institute post-doctoral fellow in White's U. laboratory when the two made their discovery in 1983.
The scientists proved that loss of one copy of a gene could unmask the version of the gene inherited from the other parent. If the unmasked gene failed to function properly, cancer would develop.
"We knew members of this family were missing a chunk of DNA from chromosome 13, but only some got retinoblastoma. In those who escaped it, the lost DNA was stuck in the middle of another chromosome," White explained.
This suggested that loss of a normal gene was allowing a defective version of the gene to take over - something that occurs in the lowly fruit fly, but had never before been seen in human cancer.
With these observations, the pair applied their technique to show that retinoblastoma is caused by loss of a particular gene on chromosome 13 that can prevent malignant transformation.
The study provided the first proof of a theory, put forward by Dr. Alfred Knudson, winner of the Mott Prize in 1988, that development of retinoblastoma and other hereditary cancers requires two genetic mishaps, each affecting one of the two copies of a particular gene.
White and Cavenee went beyond the theory to show how the gene loss triggers cancer. Their discovery proved that there are also genes that can protect against malignancy.
Using their technique, scientists are locating genes that cause deadly hereditary diseases, such as Huntington's disease, muscular dystrophy and cystic fibrosis, or those that contribute to more common illnesses such as cancer and psychiatric disorders.
White and Cavenee, and two other researchers, will receive their awards on Wednesday at the National Academy of Sciences, National Academy of Engineering Building in Washington, D.C. Each prize includes an award of $100,000 and $30,000 for a scientific workshop or conference. White and Cavenee will share the case award of the Mott Prize.