9338 results for "cancer rna-seq"

in 32.77 milliseconds.

• Long-term organoid culture of a small intestinal neuroendocrine tumor

  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our understanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit disease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal NET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage. Replicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously without dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents and as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully recapitulate many aspects of the original neuroendocrine tumor.

  Study EGAS00001007093

• METABRIC: Data from Batra et al (2021); DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation

  DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, RRBS-based profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis. After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, the study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.

  Study EGAS00001004327

• The Molecular Landscape of Asian Breast Cancers Reveals Clinically Relevant Population-Specific Differences

  Molecular profiles of breast cancer have contributed to an improved understanding of the disease, enabled development of molecular prognostic signatures to guide treatment decisions and unveiled new or more accurate therapeutic options for breast cancer patients. However, the extent to which differences in genetic, environmental and lifestyle factors influence molecular profiles in different populations remains poorly characterised, as relatively few large-scale molecular studies of breast tumours in non-Caucasian populations have hitherto been reported. Here, we present the molecular profiles of 560 Asian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to the breast tumours in predominantly Caucasian women reported in TCGA and METABRIC, we show an increased prevalence of Her2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. Using gene expression and immunohistochemistry, we observed elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst Her2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil new opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

  Study EGAS00001004518

• Identification of the genes associated with EGFR-mutant lung cancer

  To gain an insight into the genetic factors underlying the carcinogenesis of EGFR-mutant lung adenocarcinoma, we sequenced the exomes in peripheral-blood DNA from the patients.

  Study JGAS000129

• Myeloma_Targeted_Follow_up_Study

  390 samples, perform WGA, and send the WGA’d DNA to core for pre-capture library and tagging, pulldown with ELID 631172 (16 samples per reaction tube), and sequencing (24 samples per lane)

  Study EGAS00001000880

• Role_of_HPV_and_Interferon_in_APOBEC_mutational_signature

  The aim of this project is to test whether HPV oncogenes and /or interferon induce the APOBEC mutational signature in vitro, and to test the role of APOBEC3A in this process.

  Study EGAS00001002988

• Exome sequencing of patients with Ewings sarcoma

  Cancer is driven by mutations in the genome. We will uncover the mutations that give rise to Ewing's sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewing,s sarcoma tumours.

  Dataset EGAD00001000333

• Somatic pseudogenes acquired during cancer development – Whole Exome sequencing

  Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events.

  Dataset EGAD00001000637

• Somatic pseudogenes acquired during cancer development – Whole Genome sequencing

  Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events.

  Dataset EGAD00001000638

• Highly differentiated, fusion-negative rhabdomyosarcoma.

  Sequencing was performed using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 genes, previously linked to human cancer. Sequencing wa sperformed on an Illumina HiSeq 2500. 8 highly differentiated, fusion-negative rhabdomyosarcoma tumor samples were sequenced. BAM files are available for download.

  Dataset EGAD00001003887