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.
authors: Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Kenneth L
authors: KL
authors: Scott
authors: Cristina
authors: C
authors: Nogueira
authors: Timothy P
authors: TP
authors: Heffernan
authors: Remco
authors: R
authors: van Doorn
authors: Sabin
authors: S
authors: Dhakal
authors: Jason A
authors: JA
authors: Hanna
authors: Chengyin
authors: C
authors: Min
authors: Mariela
authors: M
authors: Jaskelioff
authors: Yonghong
authors: Y
authors: Xiao
authors: Chang-Jiun
authors: CJ
authors: Wu
authors: Lisa A
authors: LA
authors: Cameron
authors: Samuel R
authors: SR
authors: Perry
authors: Rhamy
authors: R
authors: Zeid
authors: Tamar
authors: T
authors: Feinberg
authors: Minjung
authors: M
authors: Kim
authors: George
authors: G
authors: Vande Woude
authors: Scott R
authors: SR
authors: Granter
authors: Marcus
authors: M
authors: Bosenberg
authors: Gerald C
authors: GC
authors: Chu
authors: Ronald A
authors: RA
authors: DePinho
authors: David L
authors: DL
authors: Rimm
authors: Lynda
authors: L
authors: Chin
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009857:Oncogenes / Q000235:genetics*; D010766:Phosphorylation; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D000071681:Tartrate-Resistant Acid Phosphatase; D046888:Tissue Array Analysis
chemical_list: D007527:Isoenzymes; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase