Journal article

Somatic Hypermutation of the YAP Oncogene in a Human Cutaneous Melanoma

Xiaomeng Zhang, Jian Zhong Tang, Ismael A Vergara, Youfang Zhang, Pacman Szeto, Lie Yang, Christopher Mintoff, Andrew Colebatch, Lachlan McIntosh, Katrina A Mitchell, Evangeline Shaw, Helen Rizos, Georgina Long, Nicholas Hayward, Grant A McArthur, Anthony T Papenfuss, Kieran F Harvey, Mark Shackleton



Melanoma is usually driven by mutations in BRAF or NRAS, which trigger hyperactivation of MAPK signaling. However, MAPK-targeted therapies are not sustainably effective in most patients. Accordingly, characterizing mechanisms that co-operatively drive melanoma progression is key to improving patient outcomes. One possible mechanism is the Hippo signaling pathway, which regulates cancer progression via its central oncoproteins YAP and TAZ, although is thought to be only rarely affected by direct mutation. As YAP hyperactivation occurs in uveal melanoma, we investigated this oncogene in cutaneous melanoma. YAP protein expression was elevated in most benign nevi and primary cutaneous melanomas ..

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Awarded by Victorian Cancer Agency (VCA) Early Career Fellowship

Awarded by National Health and Medical Research Council (NHMRC) Senior Research Fellowship

Awarded by NHMRC Program Grant

Awarded by NHMRC Senior Research Fellowship

Awarded by NHMRC

Awarded by veski

Awarded by Cancer Council of Victoria

Awarded by VCA

Funding Acknowledgements

We thank David Huang, Marco Herold, Christopher Schmidt and Karen Sheppard for cell lines and plasmids. J.Z. Tang was supported by a Victorian Cancer Agency (VCA) Early Career Fellowship (ECSG13001). K.F. Harvey was supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1078220). A.T. Papenfuss was supported by the Lorenzo and Pamela Galli Charitable Trust and by an NHMRC Program Grant (1054618) and a NHMRC Senior Research Fellowship (1116955). M. Shackleton was supported by Pfizer Australia, NHMRC (628735), veski (200910), and VCA (CRF15007) Fellowships. This research was supported by the Cancer Council of Victoria (1102820), the Victorian Cancer Biobank, the Melbourne Melanoma Project, and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Programs.