Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human melanoma progression model

ABSTRACT: Melanoma progression model

ORGANISM(S): Homo sapiens

SUBMITTER: Edward Fox

PROVIDER: E-GEOD-1792 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies.

Gallagher William M WM Bergin Orla E OE Rafferty Mairin M Kelly Zoë D ZD Nolan Ilse-Maria IM Fox Edward J P EJ Culhane Aedin C AC McArdle Linda L Fraga Mario F MF Hughes Linda L Currid Caroline A CA O'Mahony Fiona F Byrne Aileen A Murphy Alison A AA Moss Catherine C McDonnell Susan S Stallings Raymond L RL Plumb Jane A JA Esteller Manel M Brown Robert R Dervan Peter A PA Easty David J DJ

Carcinogenesis 20050615 11

The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling techniques to identify molecular determinants of melanoma progression within a unique panel of isogenic human melanoma cell lines. When a poorly tumorigenic cell line, derived from an early melanoma, was compared with two increasingly aggressive derivative cell lines, the expression of 66 genes was signi ...[more]

PMID: 15958521

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Project description:Despite advances in therapeutics, the progression of melanoma to metastasis still confers a poor outcome to patients. Nevertheless, there is a lack of biological models to understand cellular and molecular changes taking place along disease progression. Here, we analyzed the transcriptome of a multi-stage murine model of melanoma progression comprising a non-tumorigenic melanocyte lineage (melan-a), pre-malignant melanocytes (4C), non-metastatic (4C11-) and metastasis-prone (4C11+) melanoma cells. Clustering analyses have grouped the four cell lines according to their differentiated (melan-a and 4C11+) or undifferentiated/“mesenchymal-like” (4C and 4C11-) morphologies, suggesting dynamic gene expression patterns associated with the transition between these phenotypes. The cell plasticity observed in the murine melanoma progression is corroborated by molecular markers described for cell subtypes during human melanoma differentiation, as the differentiated cell lines in our model exhibit upregulation of transitory and melanocytic markers, whereas mesenchymal-like cells show increased expression of markers from undifferentiated and neural crest-like states. Sets of differentially expressed genes (DEGs) were detected at each transition step of tumor progression, and transcriptional signatures related to malignancy, metastasis and epithelial-to-mesenchymal transition were identified. Finally, DEGs were mapped to their human orthologs and subsequently evaluated in uni- and multivariate survival analysis using gene expression and clinical data of 703 drug-naïve primary melanoma patients, revealing several independent candidate prognostic markers. Altogether, these results provide novel insights into the molecular mechanisms underlying the phenotypic switch taking place during melanoma progression, reveal potential drug targets and prognostic biomarkers, and corroborate the translational relevance of this unique sequential model of melanoma progression.

Dataset Information

Transcription profiling of human melanoma progression model

Publications

Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies.

Similar Datasets

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