ORCID Profile
0000-0002-4476-9722
Current Organisation
University Health Network
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2018
DOI: 10.1200/PO.17.00248
Abstract: Fine-needle biopsy (FNB) and liquid biopsy are minimally invasive methods of tumor s ling that provide feasible means to assess tumor genotypes in real time. However, more data are needed to establish the strength of these methods by benchmarking against the current gold standard methods, core-needle biopsy (CNB) or surgical excision of the tumor. Eligible patients with advanced solid tumors were prospectively recruited. We performed mutation profiling using matched tumor DNA obtained by CNB, FNB and liquid biopsy, and matrix-assisted laser desorption/ionization time-of-flight custom mass-spectrometry or targeted next-generation DNA sequencing. The actionability of detected mutations was determined using the OncoKB Web tool. Agreement between mutations detected in CNBs, FNBs, and circulating tumor DNA (ctDNA) was examined. Forty-one patients underwent tumor biopsy. Thirty CNBs (73%) and 34 FNBs (83%) had sufficient tumor and DNA for mutation profiling. Median DNA yield from CNB and FNB were 775 ng (interquartile range, 240 to 347 4ng) and 649 ng (interquartile range, 180 to1350 ng), respectively. Of 29 CNB/FNB pairs available for comparison, actionable mutation results were concordant in 28 (96%). Six of nine actionable mutations (67%) that were found by CNB, FNB, or both were detectable in ctDNA. Two additional actionable mutations were found exclusively in ctDNA. Optimally processed FNB and liquid biopsy can be used routinely for tumor mutation profiling to identify actionable mutations.
Publisher: American Association for Cancer Research (AACR)
Date: 13-01-2023
DOI: 10.1158/1055-9965.EPI-22-0756
Abstract: The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA. The mean, SD, and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. $\\alpha $ was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component. Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and implementation studies. The logistic regression approach underestimates $\\alpha $, as compared with the RL estimates. The RL $\\alpha $ estimates were very close to those obtained by assuming proportionality to the OR per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean. BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model. : The methods described facilitate comprehensive breast cancer risk assessment.
Publisher: American Society of Hematology
Date: 07-02-2022
DOI: 10.1182/BLOODADVANCES.2021005741
Abstract: Leukemia stem cells (LSCs) are linked to relapse in acute myeloid leukemia (AML). The LSC17 gene expression score robustly captures LSC stemness properties in AML and can be used to predict survival outcomes and response to therapy, enabling risk-adapted, upfront treatment approaches. The LSC17 score was developed and validated in a research setting. To enable widespread use of the LSC17 score in clinical decision making, we established a laboratory-developed test (LDT) for the LSC17 score that can be deployed broadly in clinical molecular diagnostic laboratories. We extensively validated the LSC17 LDT in a College of American Pathologists/Clinical Laboratory Improvements Act (CAP/CLIA)-certified laboratory, determining specimen requirements, a synthetic control, and performance parameters for the assay. Importantly, we correlated values from the LSC17 LDT to clinical outcome in a reference cohort of patients with AML, establishing a median assay value that can be used for clinical risk stratification of in idual patients with newly diagnosed AML. The assay was established in a second independent CAP/CLIA-certified laboratory, and its technical performance was validated using an independent cohort of patient s les, demonstrating that the LSC17 LDT can be readily implemented in other settings. This study enables the clinical use of the LSC17 score for upfront risk-adapted management of patients with AML.
No related grants have been discovered for Tracy Stockley.