Matthew J. Wakefield
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View article: Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial
Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial Open
SOLACE2 (ACTRN12618000686202) investigates whether 12-weeks of olaparib, or cyclophosphamide-olaparib priming, improves subsequent durvalumab-olaparib progression-free survival (PFS), and is superior to olaparib monotherapy without any pri…
View article: Supplementary Table 9 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 9 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 9 summarizes the characterization of 16 SNPs associated with 23 concordant dQTLs.
View article: Data from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Data from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as tumor grade. To interrogate the evolutionary origin…
View article: Supplementary Table 2 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 2 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 2 displays results from driver selection, driver groupings and driver associations.
View article: Figure 5 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 5 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Mutational hallmarks of prostate cancer grade. A, A linear model was fit to relate each mutational density measure to ISUP GG using tumor and normal sequencing coverage as covariates. Dot size and color represents the effect size for each …
View article: Supplementary Table 7 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 7 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 7 provides summary statistics from distal dQTL associations
View article: Figure 7 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 7 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Characterization of dQTLs. A, Summary of all 35 dQTLs involving 25 unique SNPs. Dot size and color indicate the magnitude and direction of association (as OR), and background shading indicates dQTL discovered strategy. B, Forest plot of OR…
View article: Figure 4 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 4 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Mutational subtypes of localized prostate cancer. A, Mutation densities (rows) differ by ETS fusion and NKX3-1 CNA status (columns). Dot size and color gives effect-size as a Z-score, scaled to ETS-negative, NKX3-1–neutral patients. The ba…
View article: Supplementary Table 3 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 3 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 3 illustrates driver co-occurrence analysis, driver clusters, and associations of drivers with clinical features
View article: Supplementary Figures from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Figures from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Figures & Figure Legends. Supplementary Figure 1 | Cohort Structure and Analysis. Supplementary Figure 2 | CNA Evolution & Transcriptomic Effects. Supplementary Figure 3 | Properties of Driver Mutations. Supplementary Figure …
View article: Supplementary Table 4 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 4 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 4 shows driver selection for dQTL nomination and prevalence of drivers in cohorts
View article: Supplementary Table 8 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 8 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 8 shows summary statistics of 16 SNPs associated with 23 concordant dQTLs across cohorts
View article: Figure 3 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 3 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Functional characterization of driver mutations. A, Network diagrams represent multimodal pathway enrichment analysis of driver genes. Mutation types (i.e., the type of driver analysis) are indicated by shading of circles. Circle size repr…
View article: Figure 6 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 6 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
dQTLs bias somatic mutational landscape. A, Schematic of dQTL detection. The PRS used was by Schumacher and colleagues (16). Linear local dQTLs were assessed within ±500 kbp around a driver. Spatial local dQTLs were evaluated using regions…
View article: Supplementary Table 1 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 1 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 1 shows a feature-by-patient summary matrix. For each patient, this table provides version information of bioinformatics tools, summary sequencing statistics, mutational density metrics, clinical information and driver …
View article: Supplementary Table 6 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 6 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 6 displays the number of dQTLs identified for each somatic driver in each analysis strategy. Summary statistics from local dQTL associations. Statistics from logistic regression correcting for five genetic principal com…
View article: Supplementary Table 5 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 5 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 5 displays summary statistics from PRS and HOXB13 associated with somatic drivers. β and P-value from logistic regression correcting for five genetic principal components, age and somatic mutation burden. FDR = false di…
View article: Supplementary Table 10 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 10 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 10 lists dQTL SNPs identified as eQTLs in prostate tissue in GTEx.
View article: Supplementary Table 11 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Supplementary Table 11 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Supplementary Table 11 reports percentages of cross-individual contamination for each sample and sequencing lane.
View article: Figure 2 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity
Figure 2 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Somatic driver mutations in localized prostate cancer. Driver mutation discovery in 666 localized prostate tumors. The top barplot shows the distribution of the number of drivers in patients; the covariates on the left show the region type…
View article: Demethylating agents drive PARP inhibitor resistance in ovarian carcinomas with BRCA1 gene silencing
Demethylating agents drive PARP inhibitor resistance in ovarian carcinomas with BRCA1 gene silencing Open
DNA methyltransferase 1 inhibitor (DNMT1i) therapy is a promising option for increasing immune response as part of combination cancer therapy. High–grade serous ovarian carcinoma (HGSOC) is a highly aggressive cancer with poor survival out…
View article: The Germline and Somatic Origins of Prostate Cancer Heterogeneity
The Germline and Somatic Origins of Prostate Cancer Heterogeneity Open
Newly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as tumor grade. To interrogate the evolutionary origin…
View article: Generation of a PARPi-sensitive homozygous BRCA1-methylated OVCAR8 cell line using targeted CRISPR gene editing
Generation of a PARPi-sensitive homozygous BRCA1-methylated OVCAR8 cell line using targeted CRISPR gene editing Open
Up to 17% of high grade serous ovarian carcinomas (HGSOC) harbour BRCA1 promoter methylation (meBRCA1), making them susceptible to treatment with targeted PARP inhibitor (PARPi) therapy. Unfortunately, meBRCA1 loss can be acquired followin…
View article: High-level tumour methylation of <i>BRCA1</i> and <i>RAD51C</i> is required for homologous recombination deficiency in solid cancers
High-level tumour methylation of <i>BRCA1</i> and <i>RAD51C</i> is required for homologous recombination deficiency in solid cancers Open
In ovarian and breast cancer, promoter methylation of BRCA1 or RAD51C is a promising biomarker for PARP inhibitor response, as high levels lead to homologous recombination deficiency (HRD). Yet the extent and role of such methylation in ot…
View article: The role of aberrant DNA methylation in cancer initiation and clinical impacts
The role of aberrant DNA methylation in cancer initiation and clinical impacts Open
Epigenetic alterations, including aberrant DNA methylation, are now recognized as bone fide hallmarks of cancer, which can contribute to cancer initiation, progression, therapy responses and therapy resistance. Methylation of gene promoter…