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Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms.
(2018-11)
Multiple myeloma (MM) is a biologically heterogeneous malignancy, however, the mechanisms underlying this complexity are incompletely understood. We report an analysis of the whole-genome sequencing of 765 MM patients from ...
Mutational processes contributing to the development of multiple myeloma.
(NATURE PUBLISHING GROUP, 2019-08-06)
To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are ...
Measuring single cell divisions in human tissues from multi-region sequencing data.
(NATURE PUBLISHING GROUP, 2020-02-25)
Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ...
Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer.
(NATURE PORTFOLIO, 2020-05-29)
Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO ...
Subclonal reconstruction of tumors by using machine learning and population genetics.
(NATURE PUBLISHING GROUP, 2020-09-01)
Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ...
RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-01-15)
PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic ...
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...