Overlapping Tumor Suppressor Genes Independently Involved in Melanoma
Mutations in the p14ARF tumor suppressor gene (ARF) may play a role in melanoma, independent of the effect of the p16 gene.
ARF and p16 are overlapping genes at a location on chromosome 9 that is frequently mutated in melanomas. Although researchers have previously demonstrated that inactivation of the p16 tumor suppressor gene occurs frequently in melanomas, it has been less clear whether alterations in ARF occur independently of p16 in human melanoma.
In the current study, David Polsky, M.D., Ph.D., of the New York University School of Medicine and colleagues examined the two genes in 60 metastatic melanoma tumors from 58 patients.
They found two or more alterations in the ARF gene in 26 of the tumors (43 percent) and two or more alterations in the p16 gene in 13 of the samples (22 percent). In 18 tumor samples (30 percent), ARF was inactivated in the presence of the most common form of p16.
The researchers conclude that loss of ARF can promote melanoma development, even in the presence of normal p16. Human and mouse data provide strong evidence that ARF plays an important independent role in the pathogenesis of human melanoma, the authors write.
In an accompanying editorial, Gordon Peters, Ph.D., of Cancer Research UK London Research Institute provides a broad review of mouse and human data regarding the complex p16/ARF locus and melanoma. Although there are more data pointing to p16s role in melanoma, Peters concludes that researchers should not ignore ARFs possible contribution. For now, we should be content to let them share the limelight, he writes.
|Contact: Liz Savage|
Journal of the National Cancer Institute