Journal article
New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis
Cell reports (Cambridge), Vol.13(4), pp.840-853
10/27/2015
DOI: 10.1016/j.celrep.2015.09.037
PMCID: PMC5970542
PMID: 26489459
Abstract
Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA), a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases. The signature obtained was associated with phenotypic characteristics in vitro, and the core genes CAPN3 and TRIM63 were implicated in melanoma cell migration/invasion. About 90% of the melanoma signature genes belong to an intrinsic network of transcription factors governing neural development (TFAP2A, DLX2, ALX1, MITF, PAX3, SOX10, LEF1, and GAS7) and miRNAs (211-5p, 221-3p, and 10a-5p). The SCA signature effectively discriminated between two subpopulations of melanoma patients differing in overall survival, and classified MEKi/BRAFi-resistant and -sensitive melanoma cell lines.
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•Similarity core analysis (SCA) is a bioinformatics tool for analyzing expression data•SCA generates specific transcriptome-miRnome signatures for any tumor type•SCA clusters aggressive and non-aggressive tumors and cell lines•Molecular signatures reveal a lineage-specific regulatory network for melanoma
Cancer cell lines are at the forefront of drug discovery but are often limited in representing the tumor of origin due to the artificial culture conditions. Rambow et al. develop a computational approach for identifying tumor cell lineage expression cores. These core genes reveal relevant molecular dependencies linking aggressiveness, patient survival, and drug sensitivity.
Details
- Title: Subtitle
- New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis
- Creators
- Florian Rambow - Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, FranceBastien Job - Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, FranceValérie Petit - Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, FranceFranck Gesbert - Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, FranceVéronique Delmas - Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, FranceHannah Seberg - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USAGuillaume Meurice - Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, FranceEric Van Otterloo - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USAPhilippe Dessen - Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, FranceCaroline Robert - INSERM U981, Gustave-Roussy, 94805 Villejuif, FranceDaniel Gautheret - Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, FranceRobert A Cornell - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USAAlain Sarasin - Centre National de la Recherche Scientifique (CNRS) UMR8200, Gustave-Roussy and University Paris-Sud, 94805 Villejuif, FranceLionel Larue - Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.13(4), pp.840-853
- DOI
- 10.1016/j.celrep.2015.09.037
- PMID
- 26489459
- PMCID
- PMC5970542
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/27/2015
- Academic Unit
- Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research; Periodontics
- Record Identifier
- 9984025466802771
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