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Series GSE149884 Query DataSets for GSE149884
Status Public on Aug 31, 2020
Title The transcriptome of a murine model of melanoma initiation and progression unravels molecular signatures of phenotype switch and novel independent prognostic factors for melanoma patients
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design Total RNA-seq strand-oriented libraries (triplicate) from nonmalignant melanocytes (melan-a), non-tumorigenic pre-malignant melanocytes (4C), non-metastatic melanoma (4C11-) and metastatic melanoma (4C11+) were pair-sequenced (2 x 100nt) in a Illumina HiSeq 1500 platform.
Contributor(s) Reis EM, Jasiulionis MG, Pessoa DO
Citation(s) 32831131, 33845354, 35075772
Submission date May 05, 2020
Last update date May 25, 2022
Contact name Eduardo Moraes Reis
Phone +55-11-30912173
Organization name University of São Paulo
Department Biochemistry
Street address Av. Prof. Lineu Prestes, 748
City São Paulo
State/province SP
ZIP/Postal code 05508-900
Country Brazil
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (11)
GSM4516333 melan_rep2
GSM4516334 melan_rep3
GSM4516335 4c_rep1
BioProject PRJNA630432
SRA SRP260078

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE149884_RAW.tar 1.2 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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