Project description:The study includes 14 patients with confirmed JMML and known somatic mutations (from exome data of paired tumoral and germline DNA). Bone marrow or peripheral blood mononucleated cells were injected in immundeficient mice to recapitulate the leukemia. Whole exome sequencing was performed in xenograft samples to control the persistance of patients' known mutations and look for new mutations acquired in xenograft sample.
Project description:Whole exome sequencing of 5 MDS/MPN patients to identify the target of chromosome 22 acquired uniparental disomy (22aUPD). For samples E4051 and E6523, peripheral blood leucocytes (tumour) and cultured T-cells (germline) were prepared for exome sequencing using the Agilent SureSelect kit (Agilent Technologies, Palo Alto, CA, USA) (Human All Exon 50 Mb) and then sequenced on an Illumina HiSeq 2000 (Illumina, Great Abington, UK) at the Wellcome Trust Centre for Human Genetics, Oxford, UK. For samples ULSAM1182, ULSAM1242 and ULSAM1356, peripheral blood leukocyte DNA only were exome sequenced by SciLifeLab (Stockholm, Sweden).
Project description:Whole exome sequencing of 5 HCLc tumor-germline pairs. Genomic DNA from HCLc tumor cells and T-cells for germline was used. Whole exome enrichment was performed with either Agilent SureSelect (50Mb, samples S3G/T, S5G/T, S9G/T) or Roche Nimblegen (44.1Mb, samples S4G/T and S6G/T). The resulting exome libraries were sequenced on the Illumina HiSeq platform with paired-end 100bp reads to an average depth of 120-134x. Bam files were generated using NovoalignMPI (v3.0) to align the raw fastq files to the reference genome sequence (hg19) and picard tools (v1.34) to flag duplicate reads (optical or pcr), unmapped reads, reads mapping to more than one location, and reads failing vendor QC.
Project description:We developed Del-Read, an algorithm targeting medium-sized deletions (6-100 BPs) in short-reads, which are challenging for current variant callers relying on alignment. Our focus was on Micro-Homology mediated End Joining deletions (MMEJ-dels), prevalent in myeloid malignancies. MMEJ-dels follow a distinct pattern, occurring between two homologies, allowing us to generate a comprehensive list of MMEJ-dels in the exome. Using Del-Read, we identified numerous novel germline and somatic MMEJ-dels in Beat AML and TCGA-breast datasets. Validation in 500 healthy individuals confirmed their presence.
Project description:Cancer cell lines can provide robust and facile biological models for the generation and testing of hypothesis in the early stages of drug development and caner biology. Although clinical trials remain the ultimate scientific testing ground for anticancer therapies, the use of appropriate model systems to explore the molecular basis of drug activity and to identify predictive biomarkers during their development can have a profound effect on the design, cost and ultimate success of new cancer drug development. In order to capture the high degree of genomic diversity in cancer and to identify rare molecular subtypes, we have assembled a collection of >1000 cancer cell lines. These lines have been characterised using whole exome sequencing, genome wide analysis of copy number, mRNA gene expression profiling and DNA methylation analysis (http://cancer.sanger.ac.uk/cell_lines). To further characterise this panel of cell lines we have now compiled data for RNA sequencing. The current study represent data for ~450 of the cell lines in the panel, data for the remaining lines can be accessed via the CGHUB data browser hosted at UCSC. <br>This ArrayExpress record contains only meta-data. Raw data files have been archived at the European Genome-Phenome Archive (EGA, www.ebi.ac.uk/ega) by the consortium, with restricted access to protect sample donors' identity. The relevant accessions of the EGA data set is EGAD00001001357 under EGA study accession EGAS00001000828.
Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:Mutation of the gene PARK2 is the most common cause of early-onset Parkinson's Disease (PD)1,2. PARK2 encodes a gene product with E3 ubiquitin ligase activity3. In a search for multisite tumor suppressors, we identified PARK2 as a frequently targeted gene on chromosome 6q25.2-q27 in cancer. Here, we describe inactivating somatic mutations and frequent intragenic deletions of PARK2 in human malignancies. The PARK2 mutations in cancer occur in the same domains, and sometimes, at the same residues as the germline mutations causing familial PD. Cancer-specific mutations abrogate the growth suppressive effects of PARK2. PARK2 mutations in cancer decrease the gene product's E3 ligase activity, compromising its ability to ubiquitinate cyclin E and resulting in mitotic instability. These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27. PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells.