New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis.
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.
Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; Centre National de la Recherche Scientifique (CNRS) UMR3347, 91405 Orsay, France; INSERM U1021, 91405 Orsay, France; Equipe Labellisée - Ligue Nationale contre le Cancer, 91405 Orsay, France.
Florian
F
Rambow
Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, France.
Bastien
B
Job
Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; Centre National de la Recherche Scientifique (CNRS) UMR3347, 91405 Orsay, France; INSERM U1021, 91405 Orsay, France; Equipe Labellisée - Ligue Nationale contre le Cancer, 91405 Orsay, France.
Valérie
V
Petit
Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; Centre National de la Recherche Scientifique (CNRS) UMR3347, 91405 Orsay, France; INSERM U1021, 91405 Orsay, France; Equipe Labellisée - Ligue Nationale contre le Cancer, 91405 Orsay, France.
Franck
F
Gesbert
Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; Centre National de la Recherche Scientifique (CNRS) UMR3347, 91405 Orsay, France; INSERM U1021, 91405 Orsay, France; Equipe Labellisée - Ligue Nationale contre le Cancer, 91405 Orsay, France.
Véronique
V
Delmas
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
Hannah
H
Seberg
Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, France.
Guillaume
G
Meurice
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
Eric
E
Van Otterloo
Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, France.
Philippe
P
Dessen
INSERM U981, Gustave-Roussy, 94805 Villejuif, France.
Caroline
C
Robert
Plateforme de Bioinformatique, UMS AMMICA, Gustave-Roussy, 94805 Villejuif, France.
Daniel
D
Gautheret
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
Robert A
RA
Cornell
Centre National de la Recherche Scientifique (CNRS) UMR8200, Gustave-Roussy and University Paris-Sud, 94805 Villejuif, France.
Alain
A
Sarasin
Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; Centre National de la Recherche Scientifique (CNRS) UMR3347, 91405 Orsay, France; INSERM U1021, 91405 Orsay, France; Equipe Labellisée - Ligue Nationale contre le Cancer, 91405 Orsay, France. Electronic address: lionel.larue@curie.fr.
Lionel
L
Larue
D019070:Cell Lineage; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
D035683:MicroRNAs
Ewing sarcoma; breast; colon; glioblastoma; liver; lung; melanoma; miRNA; neuroblastoma; ovary; phenotype switching; survival; transcriptome