Publications by authors named "Claire A Margolis"
Article Synopsis
- - We analyzed 1,048 melanoma samples and found significant differences in their genomic characteristics based on subtypes (BRAF, (N)RAS, NF1, triple wild-type (TWT)), identifying unique secondary driver genes and mutational processes for each subtype.
- - Each melanoma subtype showed distinct patterns of dysregulated pathways and co-mutation patterns that influence their response to immune checkpoint therapies, like increased TGF-β signaling in BRAF melanomas and disrupted SWI/SNF complex in (N)RAS melanomas.
- - The study also highlighted the TWT subtype's DNA-repair defects, offering new insights into potential therapeutic approaches based on genetic profiling for treating different melanoma patient groups.
Article Synopsis
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Prior data have variably implicated the inactivation of the mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) complex with increased tumor sensitivity to immune checkpoint inhibitors (ICI). Herein, we examined the association between mSWI/SNF variants and clinical outcomes to ICIs. We correlated somatic loss-of-function (LOF) variants in a predefined set of mSWI/SNF genes (, and ) with clinical outcomes in patients with cancer treated with systemic ICIs.
View Article and Find Full Text PDFPurpose: Heterogeneity in tumor mutational burden (TMB) quantification across sequencing platforms limits the application and further study of this potential biomarker of response to immune checkpoint inhibitors (ICI). We hypothesized that harmonization of TMB across platforms would enable integration of distinct clinical datasets to better characterize the association between TMB and ICI response.
Methods: Cohorts of NSCLC patients sequenced by one of three targeted panels or by whole exome sequencing (WES) were compared (total n=7297).
Article Synopsis
- Immune-checkpoint blockade (ICB), specifically anti-PD1, has shown effectiveness in treating melanoma, but it's unclear what factors predict patient responses.
- In this study involving 144 melanoma patients, researchers found that tumor mutational burden was influenced by melanoma subtype, while new genomic and transcriptomic features, particularly related to antigen presentation, were better predictors of response.
- They also noted that previous treatment with anti-CTLA4 affected response predictors, and created models that combine clinical, genomic, and transcriptomic data to better predict which tumors might resist anti-PD1 therapy.
Purpose: Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized. We performed integrated whole-exome/transcriptome sequencing and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at time of resection (post-CRT) in 17 patients [8 complete/partial responders, 9 nonresponders (NR)].
Results: CRT was not associated with increased tumor mutational burden or neoantigen load and did not alter the distribution of established somatic tumor mutations in rectal cancer.
Article Synopsis
- Tumor mutational burden is linked to how well tumors respond to immune checkpoint therapy, but this connection is unclear in microsatellite-stable tumors.
- An analysis of 249 tumors and their normal tissue identified additional genomic factors influencing therapy response, including specific driver gene mutations and neoantigens, beyond just mutational burden.
- The findings emphasize the complexity of tumor genetics in creating an immunoresponsive environment and suggest a need for comprehensive analysis of large clinical data to find reliable predictive indicators for treatment response.
Article Synopsis
- Researchers used computer modeling to find neoepitopes, which are new immune targets, coming from intron retention events in tumor RNA.
- The study demonstrated through mass spectrometry that these retained intron neoepitopes are effectively processed and displayed on MHC I molecules in cancer cells.
- The findings suggest that these RNA-derived neoepitopes could play a significant role in developing personalized cancer vaccines in the future.
Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the gene ( = 0.
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