Author/Authors :
Scott، نويسنده , , Kenneth L. and Nogueira، نويسنده , , Cristina and Heffernan، نويسنده , , Timothy P. and van Doorn، نويسنده , , Remco and Dhakal، نويسنده , , Sabin and Hanna، نويسنده , , Jason A. and Min، نويسنده , , Chengyin and Jaskelioff، نويسنده , , Mariela and Xiao، نويسنده , , Yonghong and Wu، نويسنده , , Chang-Jiun and Cameron، نويسنده , , Lisa A. and Perry، نويسنده , , Samuel R. and Zeid، نويسنده , , Rhamy and Feinberg، نويسنده , , Tamar and Kim، نويسنده , , Minjung and Vande Woude، نويسنده , , George and Granter، نويسنده , , Scott R. and Bosenberg، نويسنده , , Marcus and Chu، نويسنده , , Gerald C. and DePinho، نويسنده , , Ronald A. and Rimm، نويسنده , , David L. and Chin، نويسنده , , Lynda، نويسنده ,
Abstract :
Summary
al 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.
