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Use of gene expression and pathway signatures to characterize the complexity of human melanoma.

Publication ,  Journal Article
Freedman, JA; Tyler, DS; Nevins, JR; Augustine, CK
Published in: Am J Pathol
June 2011

A defining characteristic of most human cancers is heterogeneity, resulting from the somatic acquisition of a complex array of genetic and genomic alterations. Dissecting this heterogeneity is critical to developing an understanding of the underlying mechanisms of disease and to paving the way toward personalized treatments of the disease. We used gene expression data sets from the analysis of primary and metastatic melanomas to develop a molecular description of the heterogeneity that characterizes this disease. Unsupervised hierarchical clustering, gene set enrichment analyses, and pathway activity analyses were used to describe the genetic heterogeneity of melanomas. Patterns of gene expression that revealed two distinct classes of primary melanoma, two distinct classes of in-transit melanoma, and at least three subgroups of metastatic melanoma were identified. Expression signatures developed to predict the status of oncogenic signaling pathways were used to explore the biological basis underlying these differential patterns of expression. This analysis of activities revealed unique pathways that distinguished the primary and metastatic subgroups of melanoma. Distinct patterns of gene expression across primary, in-transit, and metastatic melanomas underline the genetic heterogeneity of this disease. This heterogeneity can be described in terms of deregulation of signaling pathways, thus increasing the knowledge of the biological features underlying individual melanomas and potentially directing therapeutic opportunities to individual patients with melanoma.

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Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

June 2011

Volume

178

Issue

6

Start / End Page

2513 / 2522

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Pathology
  • Neoplasm Metastasis
  • Melanoma
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Databases, Genetic
  • Cluster Analysis
 

Citation

APA
Chicago
ICMJE
MLA
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Freedman, J. A., Tyler, D. S., Nevins, J. R., & Augustine, C. K. (2011). Use of gene expression and pathway signatures to characterize the complexity of human melanoma. Am J Pathol, 178(6), 2513–2522. https://doi.org/10.1016/j.ajpath.2011.02.037
Freedman, Jennifer A., Douglas S. Tyler, Joseph R. Nevins, and Christina K. Augustine. “Use of gene expression and pathway signatures to characterize the complexity of human melanoma.Am J Pathol 178, no. 6 (June 2011): 2513–22. https://doi.org/10.1016/j.ajpath.2011.02.037.
Freedman JA, Tyler DS, Nevins JR, Augustine CK. Use of gene expression and pathway signatures to characterize the complexity of human melanoma. Am J Pathol. 2011 Jun;178(6):2513–22.
Freedman, Jennifer A., et al. “Use of gene expression and pathway signatures to characterize the complexity of human melanoma.Am J Pathol, vol. 178, no. 6, June 2011, pp. 2513–22. Pubmed, doi:10.1016/j.ajpath.2011.02.037.
Freedman JA, Tyler DS, Nevins JR, Augustine CK. Use of gene expression and pathway signatures to characterize the complexity of human melanoma. Am J Pathol. 2011 Jun;178(6):2513–2522.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

June 2011

Volume

178

Issue

6

Start / End Page

2513 / 2522

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Pathology
  • Neoplasm Metastasis
  • Melanoma
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Databases, Genetic
  • Cluster Analysis