@article{59295b8d79164312a86b4ed48741a30f,
title = "Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes",
abstract = "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.",
author = "Scott, {Kenneth L.} and Cristina Nogueira and Heffernan, {Timothy P.} and {van Doorn}, Remco and Sabin Dhakal and Hanna, {Jason A.} and Chengyin Min and Mariela Jaskelioff and Yonghong Xiao and Wu, {Chang Jiun} and Cameron, {Lisa A.} and Perry, {Samuel R.} and Rhamy Zeid and Tamar Feinberg and Minjung Kim and {Vande Woude}, George and Granter, {Scott R.} and Marcus Bosenberg and Chu, {Gerald C.} and DePinho, {Ronald A.} and Rimm, {David L.} and Lynda Chin",
note = "Funding Information: Genomic studies and analyses were performed by the Belfer Institute for Applied Cancer Science. The authors wish to thank members of the Chin laboratory for helpful discussion, particularly Shan Jiang for mouse colony work and Bob Xiong for computational assistance. The authors acknowledge the generous gifts of ORF clones provided by Drs. Marc Vidal and David Hill of the human ORFeome in Center for Cancer System Biology, and the HMEL468 primed melanocytes (PMEL/hTERT/CDK4(R24C)/p53DD/BRAF V600E ) provided by Dr. David Fisher. Wide-field microscopy images for this study were acquired in the Confocal and Light Microscopy Core Facility at the Dana-Farber Cancer Institute. K.L.S. was supported by a postdoctoral fellowship from the American Cancer Society and was previously supported by a National Institutes of Health Training Grant appointment in the Department of Dermatology at Brigham and Women's Hospital, Boston. C.N. was supported by a fellowship from FCT (Praxis XXI/BD/21794/99). R.v.D. was supported by a KWF fellowship for medical specialists. This work is supported by grants from the NIH (RO1 CA93947, U01 CA84313, and P50 CA93683), and by an Established Investigator Award from the Melanoma Research Foundation to L.C. L.C. is the recipient of the Abby S. & Howard P. Milstein Innovation Award by American Skin Association. Technology/intellectual property pertaining to this manuscript has been exclusively licensed to Metamark Genetics, a development-stage molecular diagnostics company cofounded by L.C., D.L.R., and R.A.D. D.L.R. is cofounder, stockholder in, and consultant to HistoRx, the exclusive licensee of the Yale held patent on the AQUA technology that was used in this work. ",
year = "2011",
month = jul,
day = "12",
doi = "10.1016/j.ccr.2011.05.025",
language = "English (US)",
volume = "20",
pages = "92--103",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}