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Cancer Cell. 2011 Jul 12;20(1):92-103. doi: 10.1016/j.ccr.2011.05.025.

Proinvasion metastasis drivers in early-stage melanoma are oncogenes.

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  • 1Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21741599
[PubMed - indexed for MEDLINE]
PMCID:
PMC3176328
Free PMC Article
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