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Series GSE46805 Query DataSets for GSE46805
Status Public on Aug 01, 2013
Title Expression data from Uninfected and BRAF600V induced melanocytes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence, including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi.
Overall design We used RNA-Seq to detail the global programme of gene expression in primary human melanocytes which were Uninfected and BRAF600V induced cells
Contributor(s) Pawlikowski JS, McBryan T, Adams PD
Citation(s) 24043806, 26833731
Submission date May 09, 2013
Last update date May 15, 2019
Contact name Peter D. Adams
Organization name University of Glasgow, Beatson Institute for Cancer Research
Street address Switchback Rd, Bearsden
City Glasgow
ZIP/Postal code G61 1BD
Country United Kingdom
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (2)
GSM1138580 Uninfected
GSM1138581 BRAF
This SubSeries is part of SuperSeries:
GSE46818 Wnt-signaling potentiates nevogenesis.
BioProject PRJNA202399
SRA SRP022259

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Supplementary file Size Download File type/resource
GSE46805_RAW.tar 202.3 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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