7083 results for "canc*"

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• To_profile_the_landscape_of_sebaceous_tumours_WES

  Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract DNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted DNA will be used for exome sequencing.

  Study EGAS00001003553

• Amplicon_based_sequencing_of_drug_resistant_lung_cancer_cell_lines

  A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature.

  Study EGAS00001001675

• Cancer-Associated Mutations in Endometriosis without Cancer

  Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis

  Study EGAS00001003576

• Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer

  Study EGAS00001005061

• Multi-omics analysis of primary glioblastoma cell-lines shows recapitulation of pivotal molecular features of parental tumors

  Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTeX project (GBM and experimental therapeutics), a GBM-patient derived cell line library (GBM-PDCL). Multi-OMIC approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.

  Study EGAS00001001871

• Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells

  Most human breast cancers have already diversified genomically when they first become clinically evident, by which time extensive heterogeneous histopathologies, transcriptomes and growth patterns are also apparent. Accordingly, important initial events and the cellular context in which they occur have been difficult to characterize. Using DNA barcoding, we now demonstrate the high efficiency with which both purified basal and luminal cells isolated directly from normal adult human mammary tissue can be rapidly transformed by a single oncogene (KRASG12D) resulting in the production within 8 weeks in vivo of serially transplantable, polyclonal, invasive ductal carcinomas that are phenotypically heterogeneous and transcriptionally distinct from the initial cells transduced. Barcoding also revealed a consistent dramatic change in the clonal content of passaged tumours. This system thus provides a powerful new platform for examining early events in the genesis, evolution and treatment response of malignant human mammary cells generated using defined mutations.

  Study EGAS00001001310

• ENU_LS_411N_TripleTherapy

  BRAF V600E colorectal cancers do not respond to the only currently FDA approved targeted therapy for CRC. There is currently a trial underway in the UK recruiting V600E CRC patients for treatment with a triple therapy combination of Cetuximab, Trametinib and Dabrafenib. We have mutagenized a pool of V600E CRC cell lines and treated with this triple therapy to select out drug resistant clones. We will now sequence these drug resistant clones with the aim of identifying common point mutations engendering resistance to this new therapy.

  Study EGAS00001001777

• ENU_HT_29_BRAF_Triple_Therapy_Clones

  KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.

  Study EGAS00001001778

• The clonal and mutational evolution spectrum of primary triple negative breast cancers

  Primary triple negative breast cancers (TNBC) represent approximately 16% of all breast cancers and are a tumour type defined by exclusion,for which comprehensive landscapes of somatic mutation have not been determined. Here we show in 104 early TNBC cases, that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some exhibiting only a handful of somatic aberrations in a few pathways, whereas others contain hundreds of somatic events and multiple pathways implicated. Integration with matched whole transcriptome sequence data revealed that only 36% of mutations are expressed. By examining single nucleotide variant (SNV) allelic abundance derived from deep re-sequencing (median > 20,000 fold) measurements in 2414 somatic mutations, we determine for the first time in an epithelial tumour, the relative abundance of clonal genotypes among cases in the population. We show that TNBC vary widely and continuously in their clonal frequencies at the time of diagnosis, with basal subtype TNBC exhibiting more variation than non-basal TNBC. Although p53 and somatic mutations appear clonally dominant compared with other pathways, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal and cell shape/motility proteins occurred at lower clonal frequencies, suggesting they occurred later during tumour progression. Taken together our results show that future attempts to dissect the biology and therapeutic responses of TNBC will require the determination of individual tumour clonal genotypes.

  Study EGAS00001000132

• Somatic_Genetics_of_lesions_from_a_POT1_patient

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1).

  Study EGAS00001001343