5707 results for "canc*"

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• Oncogenic Ectodomain deletion of FGFR1 caused by Breakage-Fusion-Bridges in Squamous Cell lung Cancer

  The identification of recurrent 8p11.23 amplifications including FGFR1 raised the hope of a treatable target in squamous cell lung cancer (SQLC). However, only a minority of patients with FGFR1-amplified tumors respond to single agent inhibitor therapy targeting FGFR. To understand the underlying mechanism of FGFR1 dependency, we performed whole genome and transcriptome sequencing of 25 FGFR1-amplified primary tumors with unknown response upon FGFR inhibition. In addition, we performed deep sequencing of 26 FGFR1-amplified samples whereof the response upon FGFR inhibition was known for 25 samples. In both cohorts we identified intra-chromosomal tail-to-tail breaks close to the FGFR1 transcription start site, being responsible for focal amplification of FGFR1. These specific breaks are caused by a Breakage-Fusion-Bridge-like (BFB-like) mechanism. Here, we associate these breaks with FGFR inhibitor sensitivity. Moreover, in some cases these breaks are located within the open reading frame of FGFR1, which leads to the expression of an ΔEC-FGFR1 transcript that lacks the ecto-domain. Overexpression of ΔEC-FGFR1 transforms Baf3 cells and lead to an FGFR1-dependent phenotype. Our results demonstrate that the truncation of the FGFR1 ectodomain is a frequent event in 8p11.23-amplified squamous cell lung cancer caused by tail-to-tail breaks. These breaks might be used as a predictive therapeutic marker to stratify patients for FGFR-inhibitor therapy.

  Study EGAS00001005059

• Oesophageal_Adenocarcinoma_Organoid_10x

  10x Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger. This 10x data will be combined with other sequencing data in order to generate accurate reference cancer genomes.

  Study EGAS00001003191

• One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids

  Recent optimization of CRISPR/Cas9-mediated genome engineering has resulted in the development of base editors that can efficiently mediate C>T and A>G transitions. Combining these genome engineering tools with human adult stem cell (ASC)-derived organoid technology holds promise for disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived hepatocyte, endometrial and intestinal organoids. First, using conventional and evolved Cas9-variants, we show efficacy of both cytosine and adenine base editors and use them to model four hot-spot point mutations in CTNNB1 in hepatocyte organoids. Next, we apply C>T base editors in endometrial organoids to insert nonsense mutations in PTEN and demonstrate tumorigenicity even in the heterozygous state. Furthermore, we use cytosine base editors for simultaneous oncogene activation (PIK3CA) and tumor-suppressor inactivation (APC and TP53). To increase the flexibility of base editor multiplexing, we then combine SpCas9 and SaCas9 base editors for simultaneous C>T and A>G editing at individual target sites. Finally, we show the power of base editor multiplexing by modeling colorectal tumorigenesis in a single step by simultaneously transfecting sgRNA’s targeting four cancer genes. Seven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. This WGS showed, as previously reported, a genome-wide increase in C>T mutations due to C>T base editor off-target activity, which is not enriched in predicted off-target regions based on the sgRNA sequences. Furthermore, we confirmed the absence of editing-induced driver mutations and lack of off-target mutational hotspots created by the genomic engineering.

  Study EGAS00001006886

• The genomic imprint of cancer therapies helps timing the formation of metastases

  Study EGAS00001003416

• RNAseq

  RNAseq of pancreatic cancer organoids.

  Study EGAS00001007212

• TNBC ctDNA Targeted Panel

  Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) remains to be well understood. In this study, we determined the presence of early stage TNBC ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel. Sequencing of plasma DNA from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

  Study EGAS00001006937

• Colon adenomas and adenocarcinomas and matched mucosae

  Whole exome sequencing in sporadic colorectal cancers (CRC) and advanced adenomas (Ad-As), and their paired healthy mucosa, for a deeper understanding of the biology of this cancer.

  Study EGAS00001007255

• Oesophageal_Adenocarcinoma_Organoid_Hi_C

  Hi-C Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger. This Hi-C data will be combined with other sequencing data in order to generate accurate reference cancer genomes.

  Study EGAS00001003122

• X10_sequencing_of_Oesophageal_Adenocarcinoma_Organoids

  X10 Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger. This PacBio data will be combined with other sequencing data in order to generate accurate reference cancer genomes.

  Study EGAS00001003264

• Oesophageal_Adenocarcinoma_Organoids_Iso_Seq

  RNA Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger. This PacBio RNA data will be combined with other sequencing data in order to generate accurate reference cancer genomes and study how structural variants affect gene expression

  Study EGAS00001004051

• Oesophageal_Adenocarcinoma_Organoid_PacBio

  PacBio Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger. This PacBio data will be combined with other sequencing data in order to generate accurate reference cancer genomes.

  Study EGAS00001007163

• Chip_seq_oesophageal_adenocarcinoma_

  There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation. Description: Chip-seq Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.

  Study EGAS00001007180

• Adult granulosa cell tumor WGS data cohort with corresponding reference germline WGS data

  Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C>G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain  of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29-80% unique somatic mutations per sample, suggesting tumor heterogeneity. FOXL2-wildtype AGCTs had DICER1, TERT(C228T) and TP53 mutations and similar CNV profiles as FOXL2-mutant tumors. Our study confirms that absence of the FOXL2 c.402C>G mutation does not exclude AGCT diagnosis. The lack of overlapping variants in targetable cancer genes, indicates the need for personalized treatment for AGCT patients 

  Study EGAS00001004249

• Ultra-deep targeted sequencing for studying the accumulation of somatic mutations in cancer-free human skin

  Study EGAS00001004279

• PFA ependymoma cancer study

  Sequencing data related the PFA ependymoma study (Michealraj et al., Cell 2020), a lethal glial malignancy of the hindbrain found in babies and toddlers.

  Study EGAS00001004312

• Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer

  Study EGAS00001007291