Journal article

Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines

Richard J Young, Kelly Waldeck, Claire Martin, Jung H Foo, Donald P Cameron, Laura Kirby, Hongdo Do, Catherine Mitchell, Carleen Cullinane, Wendy Liu, Stephen B Fox, Ken Dutton-Regester, Nicholas K Hayward, Nicholas Jene, Alexander Dobrovic, Richard B Pearson, James G Christensen, Sophia Randolph, Grant A McArthur, Karen E Sheppard



We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was asso..

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Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

The authors wish to thank David Byrne for assistance and expertise with histology and TMA creation and acknowledge the Australian Biospecimens Network Cell Line Bank at QIMR for the provision of many of the cell lines used in this study. Pfizer Oncology and funding from the National Health and Medical Research Council of Australia Grant # 1042986 to GAM and KES financially supported this work. NKH, GAM, and RBP are all supported by fellowships from the National Health & Medical Research Council of Australia.