Early genetic evolution of driver mutations in uveal melanoma
Abstract
Abstract Uveal melanoma (UM) is an aggressive eye cancer that frequently results in metastatic death despite successful primary tumor treatment. Subclinical micrometastasis is thought to occur early, when tumors are small and difficult to distinguish from benign nevi. However, the early genetic evolution of UM is poorly understood, and biomarkers for malignant transformation are lacking. Here, we perform integrated genetic profiling of 1140 primary UMs, including 131 small tumors. A clinically available 15-gene expression profile (15-GEP) prospectively validated by our group is more accurate than driver mutations for predicting patient survival. Small tumors are significantly more likely to be in earlier stages of genetic evolution than larger tumors. Further, the 15-GEP support vector machine discriminant score predicts small tumors undergoing transformation from low-risk Class 1 to high-risk Class 2 profile. These results shed light on the early genetic evolution of UM and move us closer to a molecular definition of malignant transformation in this cancer type.
Article Details
Authors (32)
James J. Dollar
Christina L. Decatur
Ezekiel Weis
Amy C. Schefler
Miguel A. Materin
Timothy S. Fuller
Alison H. Skalet
David A. Reichstein
Ivana K. Kim
Kisha D. Piggott
Hakan Demirci
Thomas A. Aaberg
Prithvi Mruthyunjaya
Basil K. Williams
Eugene Shildkrot
Scott C. N. Oliver
Devron H. Char
Antonio Capone
John O. Mason
Scott D. Walter
Michael M. Altaweel
Jill R. Wells
Dan S. Gombos
Jay S. Duker
Peter G. Hovland
Tony Tsai
Cameron Javid
Michael A. Durante
Kyle R. Covington
Song Zhang
Zelia M. Correa
J. William Harbour