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Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2.
(CELL PRESS, 2016-08-08)
Mutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA ...
Glutathione Metabolism: An Achilles' Heel of ARID1A-Deficient Tumors.
(CELL PRESS, 2019-02-11)
In this issue of Cancer Cell, Ogiwara et al. describe a novel link between the epigenetic regulator ARID1A and glutathione metabolism in cancer that is mediated by regulation of the cystine/glutamate transporter XCT. This ...
A causal mechanism for childhood acute lymphoblastic leukaemia.
(NATURE PORTFOLIO, 2018-08-01)
In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation ...
Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data.
(PUBLIC LIBRARY SCIENCE, 2019-07-29)
Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth ...
The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia.
(NATURE PUBLISHING GROUP, 2018-09-01)
Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone ...
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.
(CELL PRESS, 2019-06-26)
Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ...
Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-08-01)
It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ...
Comparison of BEAMing and Droplet Digital PCR for Circulating Tumor DNA Analysis.
(AMER ASSOC CLINICAL CHEMISTRY, 2019-11-01)
BACKGROUND: Circulating tumor DNA (ctDNA) assays are increasingly used for clinical decision-making, but it is unknown how well different assays agree. We aimed to assess the agreement in ctDNA mutation calling between ...
Measuring Clonal Evolution in Cancer with Genomics.
(ANNUAL REVIEWS, 2019-08-31)
Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal ...
BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
(ELIFE SCIENCES PUBLICATIONS LTD, 2018-07-10)
The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding ...