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Down-Regulation of Pro-Apoptotic Genes is an Early Event in the Progression of Malignant Melanoma

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Abstract

Introduction

Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin to melanoma (thin and thick), nodal disease and distant metastases.

Methods

Twenty-eight specimens including skin (n = 1), thin melanoma (n = 6), thick melanoma (n = 7), nodal disease (n = 6), and distant metastases (n = 8), were harvested at the time of resection from 16 individuals. RNA was isolated and microarray analysis utilizing the Affymetrix GeneChip (54,000 genetic elements, U133A+B... levels) was performed. Mean level of expression was calculated for each gene within a sample group. Expression profiles were then compared between tissue groups. Student’s t-test was used to determine variance in expression between groups.

Results

We reviewed the expression of 54,000 genetic elements, of which 2,015 were found to have significantly altered expression. This represents 1,602 genes. Twenty-two pro-apoptotic genes were found to be down-regulated when compared to normal skin. Overall reduction was evaluated comparing normal skin to metastases with a range of 3.31–64.04-fold-decrease. When comparing the tissue types sequentially, the greatest fold-decrease in gene expression occurred when comparing skin to all melanomas (thin and thick) (p = 0.011). Subset analysis comparing normal skin to thin melanoma or thick melanoma, revealed the greatest component of overall reduction at the transition from thin to thick lesions (p = 0.003).

Conclusion

Sequential down-regulation of pro-apoptotic genes is associated with the progression of malignant melanoma. The greatest fold-decrease occurs in the transformation from thin to thick lesions.

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Author notes

  1. Eric H. Jensen MD

    Present address: Department of Surgery, Division of Surgical Oncology, Mayo Mail Code 195, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA

  2. Adam I. Riker MD

    Present address: University of South Alabama, Mitchell Cancer Institute, 307 North University Blvd, MSB 2015, Mobile, Alabama, 36688 0002, USA

Authors and Affiliations

  1. Department of Interdisciplinary Oncology, Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Stabile Research Building, Room 22043, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Eric H. Jensen MD, James M. Lewis MD, James M. McLoughlin MD, Michael D. Alvarado MD, Adil Daud MD, Jane Messina MD, Steven Enkemann PhD, Timothy J. Yeatman MD, Vernon K. Sondak MD & Adam I. Riker MD

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  1. Eric H. Jensen MD
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Correspondence to Adam I. Riker MD.

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Jensen, E.H., Lewis, J.M., McLoughlin, J.M. et al. Down-Regulation of Pro-Apoptotic Genes is an Early Event in the Progression of Malignant Melanoma. Ann Surg Oncol 14, 1416–1423 (2007). https://doi.org/10.1245/s10434-006-9226-2

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  • DOI: https://doi.org/10.1245/s10434-006-9226-2

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