A5068544829- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Colorectal Cancer Treatments and Studies
- Genomics and Chromatin Dynamics
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Ovarian cancer diagnosis and treatment
- BRCA gene mutations in cancer
- Renal cell carcinoma treatment
- Prostate Cancer Treatment and Research
- Bioinformatics and Genomic Networks
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA and protein synthesis mechanisms
- Genetic Mapping and Diversity in Plants and Animals
- Bladder and Urothelial Cancer Treatments
- Cancer Immunotherapy and Biomarkers
- Lymphoma Diagnosis and Treatment
- Lung Cancer Diagnosis and Treatment
- Gene expression and cancer classification
Foundation Medicine (United States)
2020-2025
Boston Foundation
2025
Jackson Laboratory
2019-2023
Tufts University
2019
Women's College Hospital
2015
Genomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management patients with advanced cancer. Beyond profiling, ctDNA also can enable calculation fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are type specific and require significant patient-level data, quantification TF potential serve as a pragmatic, tumor-agnostic tool.This study utilized cohort nationwide de-identified...
One of the great challenges in therapeutic oncology is determining who might achieve survival benefits from a particular therapy. Studies on longitudinal circulating tumor DNA (ctDNA) dynamics for prediction have generally been small or nonrandomized. We assessed ctDNA across 5 time points 466 non-small-cell lung cancer (NSCLC) patients randomized phase 3 IMpower150 study comparing chemotherapy-immune checkpoint inhibitor (chemo-ICI) combinations and used machine learning to jointly model...
To study associations across tumor types between genome-wide loss of heterozygosity (gLOH) and alterations in homologous recombination repair (HRR)-associated genes beyond BRCA1 BRCA2.
PURPOSE As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) monitoring to ICI, but uncertainty exists the generalizability these studies. Here, ctDNA ICI assessed through standardized approach by assessing clinical trial data from five independent PATIENTS AND METHODS Patient-level and were pooled harmonized 200 patients across trials...
Abstract Background Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models have focused on rare familial mutations, due to a lack frank neuropathology from based genes. Recent multi-cohort studies postmortem human brain transcriptomes identified set 30 gene co-expression modules associated with LOAD, providing molecular catalog relevant endophenotypes. Results This resource enables precise gene-based alignment between new and signatures...
PURPOSE To examine the overlap of homologous recombination deficiency (HRD) and microsatellite instability high (MSI-H) status, to dissect driver versus bystander status BRCA1/2 mutations ( BRCAm) in this context. METHODS A pan-cancer comprehensive genomic profiling cohort (n = 213,199) was examined for between BRCAm MSI-H status. variant zygosity correlated with tumor mutational burden, genome-wide loss heterozygosity (gLOH). Clinical histories two patients prostate cancer co-occurring are...
201 Background: VOPis an algorithm that predicts the cellular origin of variants, currently available on FoundationOneLiquid CDx (F1LCDx) for research use only. IMbassador250 (IM250, NCT03016312) is a completed phase III trial evaluated safety and efficacy atezolizumab in combination with enzalutamide men mCRPC who had prior progression abiraterone. Here, we prediction accuracy demonstrated clinical validity VOP IM250 samples. We hypothesized excluding predicted CH variants from maximum...
221 Background: CH results from fitness-enhancing mutations in hematopoietic stem cells that accumulate with age. Deep sequencing of LBx, a standard care for guiding therapy selection advanced PCa, can be confounded by sensitive detection variants (vars) arising both ctDNA and CH-derived DNA. Here we report the prevalence vars PCa other cancers describe an algorithmic method accurately distinguishing tumor signal, even at low variant allele frequencies (VAF). Methods: Plasma cell-free DNA...
Abstract Introduction: Distinguishing the origin of variants detected by LBx is essential as tumor-somatic and germline, but not CH variants, can provide prognostic insights inform treatment decisions. We describe a machine learning model that generates variant predictions for SVs (including base substitutions short indels) LBx. Method: For all in FoundationOne®Liquid CDx (F1LCDx) assay, VOP 3-way probability originated CH, or tumor-somatic. Tumor-somatic germline probabilities be summed to...
A majority of patients with metastatic colorectal cancer (mCRC) experience recurrence post curative-intent surgery. The addition adjuvant chemotherapy has shown to provide limited survival benefits when applied all patients. Therefore, a biomarker assess molecular residual disease (MRD) accurately and guide treatment selection is highly desirable for high-risk This feasibility study evaluated the prognostic value tissue comprehensive genomic profiling (CGP)-informed, personalized circulating...
In 2001, genetic testing for BRCA1 and BRCA2 was introduced in Ontario, women at high-risk of breast or ovarian cancer. To date over 30,000 individuals have been tested throughout Ontario. Testing offered to all Ontario residents who were eligible under any 13 criteria. We report the results tests conducted Mount Sinai Hospital from 2007 2014. A total 4726 tested, 764 (16.2%) found carry a pathogenic variant (mutation). Among 3684 men underwent without known familial BRCA mutation, 331...
Abstract Introduction: Monitoring of ctDNA can be a minimally invasive complement to tumor imaging for assessing treatment effect. Technical limitations require methods distinguish signal from clonal hematopoiesis (CH), often including non-tumor sequencing. We developed tumor-naïve panel (FoundationOne® Monitor) quantify fraction (TF). TF analytical validation used peripheral blood mononuclear cell (PBMC) then leveraged plasma collected serially patients with aNSCLC in the real-world (rw)...
Circulating tumor DNA (ctDNA) detection postoperatively may identify patients with urothelial cancer at a high risk of relapse. Pragmatic tools building off clinical next-generation sequencing (NGS) platforms could have the potential to increase assay accessibility.We evaluated widely available Foundation Medicine comprehensive genomic profiling (CGP) platform as source variants for tracking ctDNA when analyzing residual samples from IMvigor010 (ClinicalTrials.gov identifier NCT02450331),...
Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk recurrence, predicting response to therapy. Currently available tissue-informed approaches are often limited by need additional sequencing normal tissue or peripheral mononuclear cells identify non-tumor-derived alterations while tissue-naïve sensitivity. Here we present analytical validation a novel...
Cell differentiation is driven by changes in gene expression that manifest as cellular phenotype or function. Altered phenotypes, stemming from genetic mutations other perturbations, are widely assumed to directly correspond the transcriptome and vice versa. Here, we exploited cytologically well-defined Prdm9 mutant mouse a model of developmental arrest test whether parallel programs tightly coordinated, can be disassociated. By comparing cytological markers transcriptomes wild-type...
187 Background: Detection of MRD following metastatic liver resection in advanced CRC patients is associated with poor prognosis high rate relapse. Nevertheless, there currently no standard care to guide further therapy after curative intent surgery. detection has the promise be implemented into and treatment decision making. Here we establish feasibility using Foundation Medicine’s novel tissue-informed personalized monitoring assay, FoundationOne Tracker (F1T), mCRC undergoing surgical...
ABSTRACT Background Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models have focused on rare familial mutations, due to a lack frank neuropathology from based genes. Recent multi-cohort studies postmortem human brain transcriptomes identified set 30 gene co-expression modules associated with LOAD, providing molecular catalog relevant endophenotypes. Results This resource enables precise gene-based alignment between new and signatures...
Abstract Introduction: IMbassador250 was a prospective phase III international multicenter trial enrolling 759 men with mCRPC who had prior progression on abiraterone, or without taxane, randomizing to enzalutamide +/- atezolizumab. For this retrospective biomarker study, we hypothesized that decreases in ctDNA after 6 weeks of therapy, as measured from novel low-pass, whole genome methylation sequencing assay Foundation Medicine, will have greater discriminatory power distinguish overall...
The Diversity Outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity these has been well documented, epigenetic not. Epigenetic modifications, such as histone modifications DNA methylation, important regulators gene expression and, such, a critical mechanistic link between genotype phenotype. Therefore, creating map in DO is an step toward understanding mechanisms regulation to disease this resource. To end, we performed...
Abstract Introduction A common challenge presented by emerging liquid biopsy technology is to distinguish somatic variants originated in CH from those tumor. While sequencing of genomic DNA matched peripheral blood mononuclear cells (PBMC) can effectively identify variants, its wide application still remains prohibitively expensive. Computational-only solutions are challenging due shared bioinformatic presentations both and such as low allele frequency. Development algorithm with clinically...
448 Background: There is compelling rationale that detection of MRD following curative therapy may identify patients at high risk relapse requiring intensified adjuvant therapy. Combining with CGP creates an opportunity to offer MRD-guided treatment precision cancer therapeutics. Here we analyze the observation arm IMvigor-010 study understand genomics resected early stage bladder and validate CGP-informed personalized in circulating tumor DNA (ctDNA). Methods: Using tumor, tissue was...