The CancerWeb Report, What's New In Cancer: June, 1996
Cancer Genes

• Loss of the p16 gene in pituitary tumors - The pituitary gland, situated in the lower mid-front region of the brain near critical vision pathways, is a major producer of regulatory hormones for the body. Benign pituitary tumors - adenomas - are not uncommon, and their growth may not only disturb hormone balances, but also cause serious vision problems. Researchers at the Mount Sinai School of Medicine in New York described the apparent lack of functioning p16 gene in pituitary tumors in a report published in the June 1, 1996 issue of Cancer Research. They could not detect the protein product of the p16 gene in 25 samples of pituitary tumors, whereas it was present at high levels in all of 10 normal pituitary gland specimens. When looking at the p16 gene itself rather than its product, they found that it was present with no evidence for mutation, but in three samples (all macroadenomas, i.e., larger tumors) there were lower levels of the gene consistent with homozygous deletion. Whether by deletion or by another mechanism, loss of function of the p16 gene, which is considered to be a tumor suppressor, could be a significant factor in development of pituitary tumors. (Woloschak, Cancer Research 56:2493, 1996)

  Editor's Comment: - p16 has been studied extensively because it is inactivated in many human tumors as well as in human tumor- cell lines in the laboratory. Three major types of changes are responsible for loss of activity: mutation, deletion, and methylation (the insertion of a methyl group into a DNA base, usually cytosine; the issue of the impact of gene methylation is discussed in the same journal issue - Cancer Research 56:2463, 1996). p16 inhibits an enzyme that inactivates another tumor suppressor gene, the retinoblastoma gene Rb, and there is an interesting inverse relation between p16 and Rb; loss or change in one is often found together with increased amounts of the other. It is as if there is an attempt to compensate for lack of the other gene.

  ---

• The DPC4 gene, another new tumor suppressor! - Two articles in the June 1, 1996 issue of Cancer Research describe studies with the DPC4 gene, located on chromosome 18, and which was recently reported to be deleted in 30% and inactivated in another 20% of pancreatic cancers (Hahn, Science 271:350, 1996). Both articles showed that deletions or alterations in the gene occur in 10% or less of a wide range of other tumors (Kim, Cancer Research 56:2519, 1996; Schutte, Cancer Research 56:2527, 1996), suggesting that altered DPC4 does not play a major role in most kinds of cancer.