TY - JOUR
T1 - Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma
AU - Jensen, Eric H.
AU - Lewis, James M.
AU - McLoughlin, James M.
AU - Alvarado, Michael D.
AU - Daud, Adil
AU - Messina, Jane
AU - Enkemann, Steven
AU - Yeatman, Timothy J.
AU - Sondak, Vernon K.
AU - Riker, Adam I.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Gene profiling
KW - Melanoma
KW - Metastasis
KW - Microarray
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U2 - 10.1245/s10434-006-9226-2
DO - 10.1245/s10434-006-9226-2
M3 - Review article
C2 - 17195911
AN - SCOPUS:34047234687
SN - 1068-9265
VL - 14
SP - 1416
EP - 1423
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 4
ER -