Authors:
Kenneth L. Scott, Cristina Nogueira, Timothy P. Heffernan, Remco van Doorn, Sabin Dhakal, Jason A. Hanna, Chengyin Min, Mariela Jaskelioff, Yonghong Xiao, Chang-Jiun Wu, Lisa A. Cameron, Samuel R. Perry, Rhamy Zeid, Tamar Feinberg, Minjung Kim, George Vande Woude, Scott R. Granter, Marcus Bosenberg, Gerald C. Chu, Ronald A. DePinho, David L. Rimm, & Lynda Chin
Summary:
Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this deterministic hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.
Source:
Cancer Cell; Vol. 20, Issue 1, 92-103 (07/12/11)