Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes

被引：126

作者：

Scott, Kenneth L. ^{[1
,2
]}

Nogueira, Cristina ^{[1
,2
,3
]}

Heffernan, Timothy P. ^{[1
,2
]}

van Doorn, Remco ^{[2
,4
]}

Dhakal, Sabin ^{[1
,2
]}

Hanna, Jason A. ^{[5
]}

Min, Chengyin ^{[1
,2
]}

Jaskelioff, Mariela ^{[1
,2
]}

Xiao, Yonghong ^{[1
]}

Wu, Chang-Jiun ^{[1
,2
]}

Cameron, Lisa A.

Perry, Samuel R. ^{[1
]}

Zeid, Rhamy ^{[1
]}

Feinberg, Tamar ^{[1
,2
]}

Kim, Minjung ^{[1
,2
]}

Vande Woude, George ^{[6
]}

Granter, Scott R. ^{[7
]}

Bosenberg, Marcus ^{[5
]}

Chu, Gerald C. ^{[1
,2
,7
]}

DePinho, Ronald A. ^{[1
,2
]}

Rimm, David L. ^{[5
]}

Chin, Lynda ^{[1
,2
,8
]}

机构：

[1] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Univ Porto, IPATIMUP Med Fac, Inst Mol Pathol & Immunol, P-4200465 Oporto, Portugal

[4] Leiden Univ, Med Ctr, Dept Dermatol, NL-2300 RC Leiden, Netherlands

[5] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[6] Van Andel Res Inst, Grand Rapids, MI 49503 USA

[7] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA

来源：

CANCER CELL | 2011年 / 20卷 / 01期

基金：

美国国家卫生研究院;

关键词：

RESISTANT ACID-PHOSPHATASE; BREAST-CANCER; TISSUE MICROARRAYS; BONE METASTASES; CELL-MIGRATION; HOX GENES; EXPRESSION; SURVIVAL; MARKER; ACTIVATION;

D O I：

10.1016/j.ccr.2011.05.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：92 / 103

页数：12

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