BRAF/NRAS Wild-Type Melanomas Have a High Mutation Load Correlating with Histologic and Molecular Signatures of UV Damage
Victoria J Mar, Stephen Q Wong, Jason Li, Richard A Scolyer, Catriona McLean, Anthony T Papenfuss, Richard W Tothill, Hojabr Kakavand, Graham J Mann, John F Thompson, Andreas Behren, Jonathan S Cebon, Rory Wolfe, John W Kelly, Alexander Dobrovic, Grant A McArthur
CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2013
PURPOSE: The mutation load in melanoma is generally high compared with other tumor types due to extensive UV damage. Translation of exome sequencing data into clinically relevant information is therefore challenging. This study sought to characterize mutations identified in primary cutaneous melanomas and correlate these with clinicopathologic features. EXPERIMENTAL DESIGN: DNA was extracted from 34 fresh-frozen primary cutaneous melanomas and matched peripheral blood. Tumor histopathology was reviewed by two dermatopathologists. Exome sequencing was conducted and mutation rates were correlated with age, sex, tumor site, and histopathologic variables. Differences in mutations between categor..View full abstract
Awarded by Victorian Government through the Victorian Cancer Agency Translational Research Program Grant
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by Cancer Institute New South Wales
This project was enabled by the Melbourne Melanoma Project funded by the Victorian Government through the Victorian Cancer Agency Translational Research Program Grant (EOI09_27) and established through support of the Victor Smorgon Charitable Fund. This work was also supported by Program Grant 633004 of the National Health and Medical Research Council of Australia (NHMRC) and Translational Research Program Grant 10/TPG/1-02 of the Cancer Institute New South Wales. V. Mar was supported by a National Health and Medical Research Council of Australia (NHMRC) PhD Scholarship. R. A. Scolyer is supported by the Cancer Institute New South Wales Fellowship program. A. T. Papenfuss was supported by an NHMRC Career Development Fellowship with contributions also made possible through Victorian State Government Operational Infrastructure Support and NHMRC IRIISS.