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J Invest Dermatol. 2013 Nov;133(11):2585-2592. doi: 10.1038/jid.2013.197. Epub 2013 Apr 30.

Transcriptome profiling identifies HMGA2 as a biomarker of melanoma progression and prognosis.

Author information

1
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, USA. Electronic address: leonid.raskin@vanderbilt.edu.
2
Department of Dermatology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA; Department of Pathology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA.
3
Department of Pathology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA; Department of Internal Medicine, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA.
4
Department of Pathology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA.
5
Department of Dermatology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA.
6
Department of Biostatistics, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA.
7
Department of Internal Medicine, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA; Department of Epidemiology, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA; Department of Human Genetics, University of Michigan Medical School and School of Public Health, Ann Arbor, Michigan, USA; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.

Abstract

The genetic alterations contributing to melanoma pathogenesis are incompletely defined, and few independent prognostic features have been identified beyond the clinicopathological characteristics of the primary tumor. We used transcriptome profiling of 46 primary melanomas, 12 melanoma metastases, and 16 normal skin (N) samples to find genes associated with melanoma development and progression. Results were confirmed using immunohistochemistry and real-time PCR and replicated in an independent set of 330 melanomas using AQUA analysis of tissue microarray (TMA). Transcriptome profiling revealed that transcription factor HMGA2, previously unrecognized in melanoma pathogenesis, is significantly upregulated in primary melanoma and metastases (P-values=1.2 × 10(-7) and 9 × 10(-5)) compared with N. HMGA2 overexpression is associated with BRAF/NRAS mutations (P=0.0002). Cox proportional hazard regression model and log-rank test showed that HMGA2 is independently associated with disease-free survival (hazard ratio (HR)=6.3, 95% confidence interval (CI)=1.8-22.3, P=0.004), overall survival (OS) (stratified log-rank P=0.008), and distant metastases-free survival (HR=6.4, 95% CI=1.4-29.7, P=0.018) after adjusting for American Joint Committee on Cancer (AJCC) stage and age at diagnosis. Survival analysis in an independent replication TMA of 330 melanomas confirmed the association of HMGA2 expression with OS (P=0.0211). Our study implicates HMGA2 in melanoma progression and demonstrates that HMGA2 overexpression can serve as an independent predictor of survival in melanoma.

PMID:
23633021
PMCID:
PMC4267221
DOI:
10.1038/jid.2013.197
[Indexed for MEDLINE]
Free PMC Article

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