Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma

Christina Augustine, Sin Ho Jung, Insuk Sohn, Jin Soo Yoo, Yasunori Yoshimoto, John A. Olson, Henry S. Friedman, Francis Ali-Osman, Douglas Tyler

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of this study was to determine whether a single multifocal lesion is representative of residual tumor burden in terms of gene expression signatures predictive of response to therapy. Using microarray-based gene expression profiling, we examined 55 in-transit melanoma lesions across 29 patients with multifocal disease. Principal component analysis, unsupervised hierarchical clustering, one-way ANOVA, binary regression analysis, and gene signatures predictive of oncogenic pathway activation were used to compare patterns of gene expression across all multifocal lesions from a patient. Patterns of gene expression were highly similar (P < 0.006; average r = 0.979) across pretreatment lesions from a single patient compared with the significantly different patterns observed across patients (P < 0.05). The findings presented in this study show that individual melanoma tumor nodules in patients with multifocal disease harbor similar patterns of gene expression and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways, and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the use of gene expression profiling in melanoma regional therapy clinical trials to not only select optimal regional chemotherapeutic agents but to also allow for a more rational identification of candidates for specific targeted therapies and evaluation of their therapeutic efficacy. Mol Cancer Ther

Original languageEnglish (US)
Pages (from-to)779-790
Number of pages12
JournalMolecular Cancer Therapeutics
Volume9
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

Transcriptome
Melanoma
Gene Expression Profiling
Gene Expression
Therapeutics
Residual Neoplasm
Principal Component Analysis
Tumor Burden
Genes
Cluster Analysis
Neoplasms
Analysis of Variance
Regression Analysis
Clinical Trials
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma. / Augustine, Christina; Jung, Sin Ho; Sohn, Insuk; Yoo, Jin Soo; Yoshimoto, Yasunori; Olson, John A.; Friedman, Henry S.; Ali-Osman, Francis; Tyler, Douglas.

In: Molecular Cancer Therapeutics, Vol. 9, No. 4, 04.2010, p. 779-790.

Research output: Contribution to journalArticle

Augustine, C, Jung, SH, Sohn, I, Yoo, JS, Yoshimoto, Y, Olson, JA, Friedman, HS, Ali-Osman, F & Tyler, D 2010, 'Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma', Molecular Cancer Therapeutics, vol. 9, no. 4, pp. 779-790. https://doi.org/10.1158/1535-7163.MCT-09-0764
Augustine, Christina ; Jung, Sin Ho ; Sohn, Insuk ; Yoo, Jin Soo ; Yoshimoto, Yasunori ; Olson, John A. ; Friedman, Henry S. ; Ali-Osman, Francis ; Tyler, Douglas. / Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma. In: Molecular Cancer Therapeutics. 2010 ; Vol. 9, No. 4. pp. 779-790.
@article{c1bf4b00e1264009a0c41c53a342eb52,
title = "Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma",
abstract = "In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of this study was to determine whether a single multifocal lesion is representative of residual tumor burden in terms of gene expression signatures predictive of response to therapy. Using microarray-based gene expression profiling, we examined 55 in-transit melanoma lesions across 29 patients with multifocal disease. Principal component analysis, unsupervised hierarchical clustering, one-way ANOVA, binary regression analysis, and gene signatures predictive of oncogenic pathway activation were used to compare patterns of gene expression across all multifocal lesions from a patient. Patterns of gene expression were highly similar (P < 0.006; average r = 0.979) across pretreatment lesions from a single patient compared with the significantly different patterns observed across patients (P < 0.05). The findings presented in this study show that individual melanoma tumor nodules in patients with multifocal disease harbor similar patterns of gene expression and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways, and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the use of gene expression profiling in melanoma regional therapy clinical trials to not only select optimal regional chemotherapeutic agents but to also allow for a more rational identification of candidates for specific targeted therapies and evaluation of their therapeutic efficacy. Mol Cancer Ther",
author = "Christina Augustine and Jung, {Sin Ho} and Insuk Sohn and Yoo, {Jin Soo} and Yasunori Yoshimoto and Olson, {John A.} and Friedman, {Henry S.} and Francis Ali-Osman and Douglas Tyler",
year = "2010",
month = "4",
doi = "10.1158/1535-7163.MCT-09-0764",
language = "English (US)",
volume = "9",
pages = "779--790",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma

AU - Augustine, Christina

AU - Jung, Sin Ho

AU - Sohn, Insuk

AU - Yoo, Jin Soo

AU - Yoshimoto, Yasunori

AU - Olson, John A.

AU - Friedman, Henry S.

AU - Ali-Osman, Francis

AU - Tyler, Douglas

PY - 2010/4

Y1 - 2010/4

N2 - In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of this study was to determine whether a single multifocal lesion is representative of residual tumor burden in terms of gene expression signatures predictive of response to therapy. Using microarray-based gene expression profiling, we examined 55 in-transit melanoma lesions across 29 patients with multifocal disease. Principal component analysis, unsupervised hierarchical clustering, one-way ANOVA, binary regression analysis, and gene signatures predictive of oncogenic pathway activation were used to compare patterns of gene expression across all multifocal lesions from a patient. Patterns of gene expression were highly similar (P < 0.006; average r = 0.979) across pretreatment lesions from a single patient compared with the significantly different patterns observed across patients (P < 0.05). The findings presented in this study show that individual melanoma tumor nodules in patients with multifocal disease harbor similar patterns of gene expression and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways, and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the use of gene expression profiling in melanoma regional therapy clinical trials to not only select optimal regional chemotherapeutic agents but to also allow for a more rational identification of candidates for specific targeted therapies and evaluation of their therapeutic efficacy. Mol Cancer Ther

AB - In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of this study was to determine whether a single multifocal lesion is representative of residual tumor burden in terms of gene expression signatures predictive of response to therapy. Using microarray-based gene expression profiling, we examined 55 in-transit melanoma lesions across 29 patients with multifocal disease. Principal component analysis, unsupervised hierarchical clustering, one-way ANOVA, binary regression analysis, and gene signatures predictive of oncogenic pathway activation were used to compare patterns of gene expression across all multifocal lesions from a patient. Patterns of gene expression were highly similar (P < 0.006; average r = 0.979) across pretreatment lesions from a single patient compared with the significantly different patterns observed across patients (P < 0.05). The findings presented in this study show that individual melanoma tumor nodules in patients with multifocal disease harbor similar patterns of gene expression and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways, and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the use of gene expression profiling in melanoma regional therapy clinical trials to not only select optimal regional chemotherapeutic agents but to also allow for a more rational identification of candidates for specific targeted therapies and evaluation of their therapeutic efficacy. Mol Cancer Ther

UR - http://www.scopus.com/inward/record.url?scp=77950827393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950827393&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-09-0764

DO - 10.1158/1535-7163.MCT-09-0764

M3 - Article

C2 - 20371714

AN - SCOPUS:77950827393

VL - 9

SP - 779

EP - 790

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 4

ER -