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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WES

ABSTRACT: An incomplete view of the (epi)genetic events that drive melanoma initiation and progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human melanoma genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic melanoma drivers. One limitation, however, is that human melanoma genome exhibits a radically altered cytogenetic profile. Hence there is a need for biologically-meaningful approaches to identify and validate lesions that drive melanomagenesis. We combined comparative oncogenomic approaches with mouse modeling to identify new cancer genes/pathways that drive melanoma progression. Spontaneously acquired genetic alterations such as copy-number alterations and specific mutations in mouse tumors of defined genetic origin were identified and used to prioritize relevant lesions from the complex human melanoma genomes. This integrated effort confirmed the importance of several genes and pathways previously implicated in melanoma and identified new putative melanoma tumor suppressor genes. Genetic ablation of one such gene, Fes, cooperated with BRafv600E to accelerate melanomagenesis in mice. This comparative oncogenomic approach has therefore helped discover a series of novel melanoma tumor suppressor genes, including FES, with prognostic and therapeutic relevance in human melanoma.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Bram Boeckx

PROVIDER: E-MTAB-4917 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WGS part 2

Project description:An incomplete view of the (epi)genetic events that drive melanoma initiation and progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human melanoma genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic melanoma drivers. One limitation, however, is that human melanoma genome exhibits a radically altered cytogenetic profile. Hence there is a need for biologically-meaningful approaches to identify and validate lesions that drive melanomagenesis. We combined comparative oncogenomic approaches with mouse modeling to identify new cancer genes/pathways that drive melanoma progression. Spontaneously acquired genetic alterations such as copy-number alterations and specific mutations in mouse tumors of defined genetic origin were identified and used to prioritize relevant lesions from the complex human melanoma genomes. This integrated effort confirmed the importance of several genes and pathways previously implicated in melanoma and identified new putative melanoma tumor suppressor genes. Genetic ablation of one such gene, Fes, cooperated with BRafv600E to accelerate melanomagenesis in mice. This comparative oncogenomic approach has therefore helped discover a series of novel melanoma tumor suppressor genes, including FES, with prognostic and therapeutic relevance in human melanoma.

2017-05-03 | E-MTAB-5590 | biostudies-arrayexpress

Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WGS

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RNA-sequencing of Fes KO and WT melanomas

Project description:Publication abstract: An incomplete view of the (epi)genetic events that drive melanoma initiation and progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human melanoma genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic melanoma drivers. One limitation, however, is that human melanoma genome exhibits a radically altered cytogenetic profile. There is therefore the need for biologically-meaningful approaches to identify and validate lesions that drive melanomagenesis. We combined comparative oncogenomic approaches with mouse modeling to identify new cancer genes/pathways that drive melanoma progression. Spontaneously acquired genetic alterations such as copy-number alterations and specific mutations in mouse tumors of defined genetic origin were identified and used to prioritize relevant lesions from the complex human melanoma genomes. This integrated effort confirmed the importance of several genes and pathways previously implicated in melanoma and identified new putative melanoma tumor suppressor genes. Genetic ablation of one such gene, c-Fes, cooperated with BRafv600E to accelerate melanomagenesis in mice. This comparative oncogenomic approach has therefore helped discover a series of novel melanoma tumor suppressor genes, including c-FES, with prognostic and therapeutic relevance in human melanoma.

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