Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WES
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ABSTRACT:
PROVIDER: PRJEB14748 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1524210_1.fastq.gz | Fastqsanger.gz | |||
| ERR1524210_2.fastq.gz | Fastqsanger.gz | |||
| ERR1524220_1.fastq.gz | Fastqsanger.gz | |||
| ERR1524220_2.fastq.gz | Fastqsanger.gz | |||
| ERR1524211_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WGS
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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-4921 | biostudies-arrayexpress
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.
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Project description:Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WGS part 2
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Project description:<p>The purpose of the original study was to search for somatic mutations in the tyrosine kinome of serous and clear cell endometrial carcinomas (human). The study was conducted in two phases.</p> <p>Phase 1: A mutation discovery screen, in which ~577 exons encoding the catalytic domains of 86 tyrosine kinases were PCR-amplified and bidirectionally Sanger sequenced from 24 serous, 11 clear cell, and 5 mixed histology endometrial tumors. This was followed by alignment of sequence reads to the human reference sequence and subsequent nucleotide variant calling to identify potential somatic (tumor-specific) mutations. Potential somatic mutations were confirmed by re-amplification and sequencing of the relevant tumor DNA as well as matched non-tumor ("normal") DNA from the same case.</p> <p>Phase 2: A mutation prevalence screen, in which the non-catalytic regions two tyrosine kinase genes, TNK2 and DDR1, were PCR-amplified and sequenced from the 40 discovery screen tumors, and all coding exons of TNK2 and DDR1 were PCR-amplified and sequenced from another 10 clear cell, 21 serous, and 41 endometrioid endometrial tumors, in an effort to identify additional somatic mutations in each gene. Exons encoding the exonuclease domain of POLE were also sequenced to document somatic mutations.</p>
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Project description:Blood samples from patients with myeloid malignancies were analyzed using whole exome sequencing (WES). Data set from genotyping by microarray of the same samples has been deposited in ArrayExpress under accession number E-MTAB-1845 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1845/).
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