Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma

Jensen, Eric H., Lewis, James M., McLoughlin, James M., Alvarado, Michael D., Daud, Adil, Messina, Jane, Enkemann, Steven, Yeatman, Timothy J., Sondak, Vernon K. and Riker, Adam I. (2007) Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma. Annals of Surgical Oncology, 14 4: 1416-1423. doi:10.1245/s10434-006-9226-2

Author Jensen, Eric H.
Lewis, James M.
McLoughlin, James M.
Alvarado, Michael D.
Daud, Adil
Messina, Jane
Enkemann, Steven
Yeatman, Timothy J.
Sondak, Vernon K.
Riker, Adam I.
Title Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma
Journal name Annals of Surgical Oncology   Check publisher's open access policy
ISSN 1068-9265
Publication date 2007-04
Sub-type Article (original research)
DOI 10.1245/s10434-006-9226-2
Volume 14
Issue 4
Start page 1416
End page 1423
Total pages 8
Language eng
Formatted abstract
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.

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.

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).

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.
Keyword Apoptosis
Gene profiling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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