| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Article |
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
2 Department of Surgery, Division of Surgical Oncology, Mayo Mail Code 195, 420 Delaware Street, SE, Minneapolis, MN 55455, USA
3 University of South Alabama, Mitchell Cancer Institute, 307 North University Blvd, MSB 2015, Mobile, Alabama 36688 0002, USA
Correspondence: Address correspondence and reprint requests to: Adam I. Riker, MD; E-mail: ariker{at}southal.edu
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.
Key Words: Apoptosis • Melanoma • Metastasis • Gene profiling • Microarray
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
