100 research outputs found
Author Correction: Combined burden and functional impact tests for cancer driver discovery using DriverPower
No full textAuthor Correction: High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations
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Navigating the Cancer Transcriptome by Decoding Divergent Oncogenic States.
No full textA new approach decomposes aberrant signaling mediated by an oncogenic mutation into underlying core cellular states that may be more permissive to available therapeutic options. Cell Syst 2017 Aug 23; 5(2):1978-1990
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues.
No full textHistone modifications constitute a major component of the epigenome and play important regulatory roles in determining the transcriptional status of associated loci. In addition, the presence of specific modifications has been used to determine the position and identity non-coding functional elements such as enhancers. In recent years, chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) has become a powerful tool in determining the genome-wide profiles of individual histone modifications. However, it has become increasingly clear that the combinatorial patterns of chromatin modifications, referred to as Chromatin States, determine the identity and nature of the associated genomic locus. Therefore, workflows consisting of robust high-throughput (HT) methodologies for profiling a number of histone modification marks, as well as computational analyses pipelines capable of handling myriads of ChIP-Seq profiling datasets, are needed for comprehensive determination of epigenomic states in large number of samples. The HT-ChIP-Seq workflow presented here consists of two modules: 1) an experimental protocol for profiling several histone modifications from small amounts of tumor samples and cell lines in a 96-well format; and 2) a computational data analysis pipeline that combines existing tools to compute both individual mark occupancy and combinatorial chromatin state patterns. Together, these two modules facilitate easy processing of hundreds of ChIP-Seq samples in a fast and efficient manner. The workflow presented here is used to derive chromatin state patterns from 6 histone mark profiles in melanoma tumors and cell lines. Overall, we present a comprehensive ChIP-seq workflow that can be applied to dozens of human tumor samples and cancer cell lines to determine epigenomic aberrations in various malignancies
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
No full textauthor correctio
Author Correction: Combined burden and functional impact tests for cancer driver discovery using DriverPower
No full textIn the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortiumwere listed in the Supplementary Information; however, these members shouldhave been included in themainpaper.The originalArticle has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. In the PCAWG Drivers and Functional Interpretation Group, the affiliation for Erik Larsson has also been changed from ‘Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.’ to ‘Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden’. Additional corrections to affiliations and author names have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper
Molecular and clonal evolution in recurrent metastatic gliosarcoma.
No full textWe discuss the molecular evolution of gliosarcoma, a mesenchymal type of glioblastoma (GBM), using the case of a 37-yr-old woman who developed two recurrences and an extracranial metastasis. She was initially diagnosed with isocitrate dehydrogenase (IDH) wild-type gliosarcoma in the frontal lobe and treated with surgery followed by concurrent radiotherapy with temozolomide. Five months later the tumor recurred in the left frontal lobe, outside the initially resected area, and was treated with further surgery and radiotherapy. Six months later the patient developed a second left frontal recurrence and was again treated with surgery and radiotherapy. Six weeks later, further recurrence was observed in the brain and bone, and biopsy confirmed metastases in the pelvic bones. To understand the clonal relationships between the four tumor instances and the origin of metastasis, we performed whole-genome sequencing of the intracranial tumors and the tumor located in the right iliac bone. We compared their mutational and copy-number profiles and inferred the clonal phylogeny. The tumors harbored shared alterations in GBM driver genes, including mutations in TP53, NF1, and RB1, and CDKN2A deletion. Whole-genome doubling was identified in the first recurrence and the extracranial metastasis. Comparisons of the metastatic to intracranial tumors highlighted a high similarity in molecular profile but contrasting evidence regarding the origin of the metastasis. Subclonal reconstruction suggested a parallel evolution of the recurrent tumors, and that the metastatic tumor was largely derived from the first recurrence. We conclude that metastasis in glioma can be a late event in tumorigenesis
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