15153 results for "cancer studies using rna-seq"

in 47.69 milliseconds.

• Identification of driver oncogenes in scirrhous-type gastric cancer cell lines

  Scirrhous type gastric cancer (SGC) is one of the most intractable cancer subtypes in human, and its therapeutic targets have been rarely identified to date. Exploration of somatic mutations in the SGC genome with the next generation sequencers has been hampered by low tumor contents by the markedly increased fibrous tissues. Thus, SGC cell lines may be useful resources to search for novel oncogenes in. Here we have conducted whole exome sequencing and RNA sequencing on two SGC cell lines, OCUM-8 and OCUM-9. Interestingly, most of the mutations thus identified have not been reported. In OCUM-8 cells, a novel CD44-IGF1R fusion gene is discovered, the protein product of which ligates the amino-terminus of CD44 to the transmembrane and the tyrosine-kinase domains of IGF1R. Further, both of CD44 and IGF1R are markedly amplified in the OCUM-8 genome and abundantly expressed. CD44-IGF1R has a transforming ability, and the suppression of its kinase activity leads to rapid cell death of OCUM-8. On the other hand, OCUM-9 seems to possess multiple oncogenic events in its genome. The MET gene is highly amplified, and the treatment of OCUM-9 with crizotinib, a MET inhibitor, results in cell death. Further, a novel BORCS5-ETV6 fusion gene is identified in the OCUM-9 genome. BORCS5-ETV6 possesses oncogenic activity, and suppression of its message partially inhibits cell growth. Prevalence of these novel fusion genes among SGC awaits further investigation, but we validate the significance of cell lines as appropriate reagents for detailed genomic analyses of SGC.

  Study JGAS000179

• Biallelic tumor suppressor loss and DNA repair defects in de novo small cell prostate cancer

  Small cell prostatic carcinoma (SCPC) is an aggressive pathology that is managed similar to small cell lung cancer. SCPC can evolve from prostatic adenocarcinoma in response to androgen deprivation therapy but in rare cases is present at initial cancer diagnosis. The molecular etiology of de novo SCPC is incompletely understood due to the scarcity of tumor tissue and the brief life expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology and the remainder had some admixed adenocarcinoma foci, but all were treated with first line platinum-based chemotherapy. Median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin embedded archival tumor tissue. We observed frequent biallelic deletion and/or mutation of tumor suppressors TP53, RB1 and PTEN, similar to treatment related SCPC. Indeed, at the RNA level pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes including BRCA1, BRCA2, ATM and MSH2/6: potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harbored ETS gene rearrangements to androgen-driven promoters, consistent with evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape underlies this unusual pathologic variant, and propose opportunities for targeted therapy strategies in a disease with few treatment options.

  Study EGAS00001003007

• Colorectal cancer organoids expressing BRAF (fusion) genes

  Fusion genes may be oncogenic drivers and potential targets for personalized therapies in a variety of cancer types. The BRAF gene is frequently involved in oncogenic fusions, with fusion frequencies of 0.2-3% throughout different cancers. BRAF can be fused to a wide variety of genes, however, BRAF fusions rarely occur in the exact same gene configuration, making assessment of the fusion relevance and decision for drug treatment challenging. Here, we devised a colorectal cancer organoid-based platform to functionally characterize diverse BRAF fusions, containing various partner genes (AGAP3, DLG1 and TRIM24). We compared these BRAF fusions with respect to cellular behaviour, downstream signaling activation and response to targeted therapies. We found that 5’ partner choice of BRAF affects cellular localization and intracellular signaling capacities of the fusion genes. The DLG1-BRAF fusion gene showed distinct localization to the plasma membrane and exhibited increased levels of MAPK pathway activation under unperturbed conditions. Furthermore, the different BRAF fusions showed varying sensitivities to the targeted inhibition of ERK and BRAF, with the DLG1-BRAF fusion being the most sensitive. Additionally, RNA-sequencing identified distinct subsets of genes affected by the DLG1-BRAF fusion gene. Importantly, all fusion genes conveyed resistance to the clinically relevant EGFR/HER2/HER4-inhibitor afatinib, suggesting that BRAF fusions should be screened alongside other MAPK pathway alterations to identify mCRC patients amenable to cetuximab treatment. In summary, we developed a platform to efficiently assess molecular and cellular effects of fusion genes, and revealed that differential drug responses and distinct gene expression profiles can be induced by different BRAF fusions .

  Study EGAS00001003558

• Total RNA sequencing of RNA from testicular tissue

  Study EGAS00001006119

• ICGC MMML-seq Data Freeze November 2012 whole genome sequencing

  ICGC MMML-seq Data Freeze November 2012 whole genome sequencing

  Dataset EGAD00001000278

• ICGC MMML-seq Data Freeze November 2012 whole exome sequencing

  ICGC MMML-seq Data Freeze November 2012 whole exome sequencing

  Dataset EGAD00001000279

• ICGC MMML-seq Data Freeze March 2013 whole genome sequencing

  ICGC MMML-seq Data Freeze March 2013 whole genome sequencing

  Dataset EGAD00001000355

• ICGC MMML-seq Data Freeze July 2013 transcriptome sequencing

  ICGC MMML-seq Data Freeze July 2013 transcriptome sequencing

  Dataset EGAD00001000648

• EM-seq converted WGS for CSF-derived cfDNA from pediatric brain tumor patients

  EM-seq converted WGS for CSF-derived cfDNA from pediatric brain tumor patients

  Dataset EGAD50000001975

• Patient data used in FLTseq paper

  Apply newly developed FLT-seq protocol and package FLAMES on a primary patient sample

  Study EGAS00001005597

• Reference epigenome Pancreas-Islet07 input ChIP-Seq data generated from KEP study

  Pancreas-Islet07 input ChIP-Seq paired end data

  Dataset EGAD00001007463

• Reference epigenome IPS-NPC02 input ChIP-Seq data generated from KEP study

  IPS-NPC02 input ChIP-Seq paired end data

  Dataset EGAD00001007290

• Reference epigenome Pancreas-Islet07 h3k9me3 ChIP-Seq data generated from KEP study

  Pancreas-Islet07 h3k9me3 ChIP-Seq paired end data

  Dataset EGAD00001007462

• Reference epigenome Pancreas-Islet02 h3k9me3 ChIP-Seq data generated from KEP study

  Pancreas-Islet02 h3k9me3 ChIP-Seq paired end data

  Dataset EGAD00001007198

• Reference epigenome Pancreas-Islet02 input ChIP-Seq data generated from KEP study

  Pancreas-Islet02 input ChIP-Seq paired end data

  Dataset EGAD00001007199

• Reference epigenome Kidney-mesangial02 h3k36me3 ChIP-Seq data generated from KEP study

  Kidney-mesangial02 h3k36me3 ChIP-Seq paired end data

  Dataset EGAD00001007258

• Reference epigenome Pancreas-Islet03 h3k27ac ChIP-Seq data generated from KEP study

  Pancreas-Islet03 h3k27ac ChIP-Seq paired end data

  Dataset EGAD00001007200

• Reference epigenome Pancreas-Islet03 h3k27me3 ChIP-Seq data generated from KEP study

  Pancreas-Islet03 h3k27me3 ChIP-Seq paired end data

  Dataset EGAD00001007201

• Reference epigenome Fat-Preadipocyte01 h3k36me3 ChIP-Seq data generated from KEP study

  Fat-Preadipocyte01 h3k36me3 ChIP-Seq paired end data

  Dataset EGAD00001007223

• Reference epigenome Fat-Preadipocyte01 h3k4me3 ChIP-Seq data generated from KEP study

  Fat-Preadipocyte01 h3k4me3 ChIP-Seq paired end data

  Dataset EGAD00001007225