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MITF-low zebrafish melanomas reveal cells with no MITF activity at the site of residual disease

ABSTRACT: MITF-low zebrafish melanomas reveal cells with no MITF activity at the site of residual disease

PROVIDER: PRJNA533623 | ENA |

REPOSITORIES: ENA

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MITF-low zebrafish melanomas reveal cells with no MITF activity at the site of residual disease

Project description:The MITF-low melanoma transcriptional signature is predictive of poor outcome for patients but little is known about its biological signature. We used genetic models of zebrafish with low expression of mitfa (MITF-low) to study this biological subtype. We performed whole bulk RNA-seq to classify zebrafish MITF-low melanoma that cluster mainly by their directionality of growth and assess their resemblance to patients’ MITF-low subgroups. Furthermore, using genetic inhibition of MITF activity we discover minimal residual disease at the site of regression and using single-cell and low input RNA-seq we characterise these MITF independent cells and show that they pre-exist in the primary tumour.

2019-10-09 | GSE130037 | GEO

MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease

Project description:The MITF-low melanoma transcriptional signature is predictive of poor outcome for patients but little is known about its biological signature. We used genetic models of zebrafish with low expression of mitfa (MITF-low) to study this biological subtype. Using genetic inhibition of MITF activity we discover minimal residual disease at the site of regression. We performed single cell RNA-seq (Smart-seq2) to characterise cells at the site of residual disease, and put in relation with primary tumours and recurring disease.

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MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease

Project description:MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease

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Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease.

Project description: Not available

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Expression analysis of zebrafish melanoma and skin from the mitf-BRAFV600E;p53-/- line

Project description:Investigation of expression differences between skin and melanomas from a transgenic BRAFV600E zebrafish model of melanoma The embryos described in this study are further analyzed in a manuscript submitted for publication by White, et al. A 15 chip study using RNA extracted from either WT zebrafish skin, mitf-BRAFV600E;p53-/- skin or mitf-BRAFV600E;p53-/- melanoma

2011-03-30 | E-GEOD-24528 | biostudies-arrayexpress

Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma

Project description:Increased MITF expression contributes to melanoma progression and resistance to BRAF pathway inhibition. We show that, unexpectedly, lack of MITF is associated with more severe resistance to a range of inhibitors. Indeed, the presence of endogenous MITF was essential for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlated with expression of several activated receptor tyrosine kinases, most commonly AXL. The MITF-low/AXL-high/drug resistance phenotype was seen in roughly half of BRAF mutant and the majority of NRAS mutant melanoma cell lines. The dichotomous behavior of MITF in drug response was corroborated in vemurafenib-resistant biopsies, including MITF high and low clones in a relapsed patient. Drug cocktails containing AXL inhibitor enhanced melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas. Experssion analysis by RNAseq of 14 melanoma cell lines.

2014-09-19 | E-GEOD-61544 | biostudies-arrayexpress

Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma

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Expression analysis of transgenic embryos carrying the mitf-BRAFV600E allele in the presence or absence of p53 function

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MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma

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Differential gene expression of zebrafish melanocytes and melanomas (microarray)

Project description:We report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas.

2018-02-14 | GSE83399 | GEO

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