First cancer-protecting gene characterized.

First cancer-protecting gene characterized

Boston-area researchers have identified a gene whose disruption leads to retinoblastoma, a rare eye cancer. They have also developed a way to test for the presence of the normal gene, which is expected to help in prenatal diagnosis.

Human genes analogous to genes known to cause cancer in animals have been identified, and these same human genes cause cancerous changes when transferred to cultured cells or to rodents. But the current work is the first to characterize a genetic deletion that causes cancer in humans. The retinoblastoma defect, localized by researchers from the Whitehead Institute for Biomedical Research, Harvard Medical School and Massachusetts Eye and Ear Infirmary, has been the object of a search by several other groups as well.

Retinoblastomas develop in the retinas of young children and can, if caught in time, be treated by removing affected eyes. Previous research has traced the tumors to the absence of a section of chromosome 13. Since developed cells have two copies of each chromosome, initiation of the tumor requires either a mutation in both genes or an inherited problem in one chromosome 13 plus the loss or mutation of the other (SN: 1/5/85, p.10).

In the Oct. 16 NATURE the researchers describe isolating a piece of chromosome 13 DNA that they then used as a probe. The DNA probe matched up with genetic material from normal retinal cells and cells from other tumors, but not retinoblastoma cells. They also determined the size and location of the corresponding segment in the normal gene.

The probe can be used to determine if a person has inherited the retinoblastoma potential and thus could pass it on, or if it resulted from a chance mutation, says Massachusetts Eye and Ear's Thaddeus P. Dryja. The presence of the matching section on only one of the chromosome 13s in cells from other body parts means that the person probably inherited a defective gene and developed retinoblastoma when the remaining normal gene in a retinal cell mutated. If other cells have two normal copies, the retinoblastoma arose from chance mutations in both chromosomes of a retinal cell, and is not not in the germ line and thus not inheritable.

The probe can also be used for early or prenatal detection of the defect, allowing early, possibly eye-saving treatment. Next in line, says Dryja, will be determining the structure and function of the protein engineered by the gene.

Retinoblastoma affects only 200 or so children in the United States a year. Webster Cavenee of the Ludwig Institute for Cancer Research in Montreal, who with colleagues determined several years ago that retinoblastomas resulted from the absence of a normal copy of the gene, says the current work may influence more than just retinoblastoma research. While much cancer research has focused on dominant genes whose presence cause cancer, his laboratory and others have found many tumors that, like retinoblastoma, are linked to recessive genes whose absence leads to cancer.

Says Cavenee, "I think the answers that will come out of [the retinoblastoma work] are going to be expandable to a wide range of human cancers, and maybe most of them.'