Nature Genetics37, 745 - 749 (2005)
Published online: 12 June 2005; | doi:10.1038/ng1586
Use of human tissue to assess the oncogenic activity of melanoma-associated mutations
Yakov Chudnovsky1, 2, Amy E Adams1, 2, Paul B Robbins1, Qun Lin1
& Paul A Khavari1
1
Veterans Affairs Palo Alto Healthcare System, Palo Alto, California 94304, USA and Program in Epithelial Biology, Stanford University School of Medicine, 269 Campus Drive, Room 2145, Stanford, California
94305, USA.
Multiple genetic alterations occur in melanoma, a lethal skin malignancy of increasing incidence1,
2. These include mutations that activate Ras and two of its effector cascades, Raf and phosphoinositide 3-kinase (PI3K). Induction of Ras and Raf can be caused by active N-Ras and B-Raf mutants as well as by gene amplification3,
4,
5. Activation of PI3K pathway components occurs by PTEN loss and by AKT3 amplification6,
7,
8. Melanomas also commonly show impairment of the p16INK4A-CDK4-Rb and ARF-HDM2-p53 tumor suppressor pathways. CDKN2A mutations can produce p16INK4A and ARF protein loss5,
9,
10,
11. Rb bypass can also occur through activating CDK4 mutations as well as by CDK4 amplification5,
12. In addition to ARF deletion, p53 pathway disruption can result from dominant negative TP53 mutations5,
13. TERT amplification also occurs in melanoma5. The extent to which these mutations can induce human melanocytic neoplasia is unknown. Here we characterize pathways sufficient to generate human melanocytic neoplasia and show that genetically altered human tissue facilitates functional analysis of mutations observed in human tumors.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
