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Open AccessThe methyltransferase domain of DNMT1 is an essential domain in acute myeloid leukemia independent of DNMT3A mutation
Aberrant DNA methylation patterns are a prominent feature of cancer. Methylation of DNA is mediated by the DNA methyltransferase (DNMT) protein family, which regulates de novo (DNMT3A and DNMT3B) and maintenance ...
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Article
Next-generation characterization of the Cancer Cell Line Encyclopedia
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets...
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Article
Small-molecule targeting of brachyury transcription factor addiction in chordoma
Chordoma is a primary bone cancer with no approved therapy1. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutati...
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Article
Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells
CERES is a new computational method to estimate gene-dependency levels from CRISPR–Cas9 essentiality screens while accounting for copy number effects and variable sgRNA activity. Applying CERES to new genome-s...
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Article
Characterizing genomic alterations in cancer by complementary functional associations
Complementary genomic features associated with pathway activation, gene dependency and drug sensitivity are uncovered using REVEALER.
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Article
High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines
A method called PRISM rapidly identifies drug candidates that are effective against specific cancer cell lines.
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Article
Erratum: Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies
Scientific Data 1:140035 doi: 10.1038/sdata.2014.35 (2014); Published 30 September 2014; Updated 11 November 2014 The original version of this Data Descriptor contained a typographical error in the spelling of...
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Article
Open AccessParallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies
Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viabi...
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Article
Absolute quantification of somatic DNA alterations in human cancer
Tumors vary in their ratio of normal to cancerous cells and in their genomic copy number. Carter et al. describe an analytic method for inferring the purity and ploidy of a tumor sample, enabling longitudinal stu...
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Article
Towards patient-based cancer therapeutics
Orienting cancer drug discovery to the patient requires relating the genetic features of tumors to acquired gene and pathway dependencies and identifying small-molecule therapeutics that target them.
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Article
Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy
Samuel Singer and colleagues report an integrative genomic analysis of soft-tissue sarcomas. They survey sequence, copy number and mRNA expression in 207 individuals diagnosed with one of seven major high-grad...
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Article
The landscape of somatic copy-number alteration across human cancers
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-...
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Article
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Mutations in genes of the RAS family are preset on about 20% of human cancers, making RAS proteins prime potential targets for cancer therapy. Direct targeting of RAS proteins has not so far been productive, but ...
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Article
SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas
Matthew Meyerson and colleagues report that SOX2, which encodes a transcription factor necessary for normal esophageal development, is an amplified lineage survival oncogene in lung and esophageal squamous cell c...
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Article
Somatic mutations affect key pathways in lung adenocarcinoma
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to disco...
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Open AccessMajor copy proportion analysis of tumor samples using SNP arrays
Single nucleotide polymorphisms (SNPs) are the most common genetic variations in the human genome and are useful as genomic markers. Oligonucleotide SNP microarrays have been developed for high-throughput geno...
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Article
Open AccessCharacterizing the cancer genome in lung adenocarcinoma
A wide-ranging overview of genetic alterations in lung adenocarcinomas, published in this issue, takes a new approach to genome analysis. The analysis of 371 tumours revealed 31 recurrent focal events, only si...
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Targeted Brownfields Assessment of a Former Power Plant Using the Triad Approach
A Targeted Brownfields Assessment of a former power plant was conducted using the Triad approach, through the efforts of EPA Region I and Metcalf & Eddy, the Brownfields Technology Support Center, and the town...