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

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

Research output: Contribution to journalReview article

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1416-1423
Number of pages8
JournalAnnals of Surgical Oncology
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Melanoma
Down-Regulation
Skin
Genes
Neoplasm Metastasis
Gene Expression
Microarray Analysis
Oligonucleotide Array Sequence Analysis
RNA
Apoptosis
Students

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma. / Jensen, Eric H.; Lewis, James; Mcloughlin, James; Alvarado, Michael D.; Daud, Adil; Messina, Jane; Enkemann, Steven; Yeatman, Timothy J.; Sondak, Vernon K.; Riker, Adam I.

In: Annals of Surgical Oncology, Vol. 14, No. 4, 01.04.2007, p. 1416-1423.

Research output: Contribution to journalReview article

Jensen, EH, Lewis, J, Mcloughlin, J, Alvarado, MD, Daud, A, Messina, J, Enkemann, S, Yeatman, TJ, Sondak, VK & Riker, AI 2007, 'Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma', Annals of Surgical Oncology, vol. 14, no. 4, pp. 1416-1423. https://doi.org/10.1245/s10434-006-9226-2
Jensen, Eric H. ; Lewis, James ; Mcloughlin, James ; Alvarado, Michael D. ; Daud, Adil ; Messina, Jane ; Enkemann, Steven ; Yeatman, Timothy J. ; Sondak, Vernon K. ; Riker, Adam I. / Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma. In: Annals of Surgical Oncology. 2007 ; Vol. 14, No. 4. pp. 1416-1423.
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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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T1 - Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma

AU - Jensen, Eric H.

AU - Lewis, James

AU - Mcloughlin, James

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.

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Y1 - 2007/4/1

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.

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