Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology

Rasmussen, Samuel; Jin, Jia Xiang; Bickford, Lissett R.; Woods, Andrew D; Sahm, Felix; Crawford, Kenneth A.; Nagamori, Kiyo; Goto, Hiroaki; Torres, Keila E.; Sidoni, Angelo; Rudzinski, Erin R.; Thway, Khin; Jones, Robin L.; Ciulli, A.; Wright, Hollis; Lathara, Melvin; Srinivasa, Ganapati; Kannan, Kavya; Huang, Paul H.; Grünewald, Thomas G.P.; Berlow, Noah; Keller, Charles

doi:10.1002/ctm2.961

Cited by 8 publications

(5 citation statements)

References 49 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the 2020 World Health Organization classification of soft tissue tumors, there exist 2 distinct subtypes of ES, the classic "distal" variant and the "proximal" variant, of which proximal ES occurs more in older adults, near the trunk and portends a less favorable prognosis due to more aggressive disease. 5,14,15 The classic-distal and proximal types can each occur in proximal or distal sites and may each show features of both types. 16 The distinction between the variants is defined primarily by histologic findings irrespective of demographics or tumor location.…”

Section: Discussionmentioning

confidence: 99%

Metastatic Epithelioid Sarcoma of the Eyelid in a 47-Year-Old Man: A Case Report

Han¹,

Dermarkarian²,

Camacho³

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

View full text Add to dashboard Cite

Epithelioid sarcoma is a rare soft tissue neoplasm of uncertain differentiation that typically affects the distal extremities. Primary orbital epithelioid sarcoma is rare, and no reports exist characterizing metastases of this tumor to the orbit and ocular adnexa. In this article, the authors describe a rare case of eyelid metastasis in a 47-year-old man with epithelioid sarcoma of the right fibula diagnosed 16 months earlier who was otherwise doing well on the adjuvant tazemetostat therapy. In addition, the authors perform a retrospective review of cases of primary orbital epithelioid sarcoma reported in the literature, of which 4 patients responded favorably to surgical excision whereas 2 others eventually died as a direct result of their disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Metastatic Epithelioid Sarcoma of the Eyelid in a 47-Year-Old Man: A Case Report

Han¹,

Dermarkarian²,

Camacho³

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

View full text Add to dashboard Cite

show abstract

“…Sequencing was performed by BGI using the DNBSeq G400 sequencer and by Novogene using the Illumina NovaSeq6000 sequencer, and data were analyzed using previously established analysis pipelines based on best practices 39 , 40 , 43 , 44 . In brief, raw FASTQ sequencing files from DNA sequencing experiments were quality control-filtered using SOAPnuke v.2.1.8 (ref.…”

Section: Methodsmentioning

confidence: 99%

Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers

Acanda De La Rocha,

Berlow,

Fader

et al. 2024

Nat Med

Self Cite

View full text Add to dashboard Cite

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376.

show abstract

“…FFPE tissues were shipped to BGI at ambient temperatures in an independent package. Sequencing data provided by BGI were analyzed using previously established analysis pipelines [79][80][81][82] . In brief, raw FASTQ sequencing les from DNA sequencing were quality control ltered via SOAPnuke 83 and aligned to the GRCh38 human reference genome using BWA MEM aligner 84 .…”

Section: Hierarchical Clustering and Spearman Correlation Coe Cient A...mentioning

confidence: 99%

“…The explainable AI/ML (xAI/ML) platform to identify causal pharmacogenomic biomarkers of drug response is adapted from the PTIM-Circuit personalized combination platform 81,82 and the PTM-Biomarker analysis platform 79,91 . In brief, patient-derived DSS pro les and whole exome and whole transcriptome sequencing data were ingested into the xAI/ML framework to generate multi-omics relationships differentiating ex vivo drug sensitivity.…”

Section: Explainable Ai/ml Biomarker Analysismentioning

confidence: 99%

Functional Precision Medicine Enhances Clinical Outcomes of Relapsed/Refractory Pediatric and Adolescent Cancer Patients

Azzam,

Rocha,

Berlow

et al. 2023

Preprint

View full text Add to dashboard Cite

Current genomics-driven precision oncology identifies actionable mutations in < 10% of cancer patients. Pediatric cancer is especially challenging due to limited mutations and fewer genomics-guided options. Functional precision medicine (FPM) addresses this by integrating genomic profiling with rapid, high-throughput functional ex vivo drug testing on live patient-derived cells. However, there is lack of FPM prospective data showing clinical utility in pediatric cancers. In this prospective, non-randomized, single-arm study (NCT03860376), we investigated feasibility and impact of FPM in pediatric/adolescent with refractory/relapsed solid and hematologic cancers. Of 25 patients, 19 (76%) had FPM data reviewed by the FPM tumor board within four weeks (FPMTB), meeting the primary outcome of the study. Additionally, six patients received FPM-guided treatment. Among these 6 patients, 83% (5 patients) experienced a greater than 1.3-fold improved progression-free survival compared to their previous therapy, and together demonstrated a significant increase in progression-free survival and objective response rate versus physician’s choice-treated patients (8 patients). Post-hoc analysis showed that patients with the same subtype of cancer do not cluster together, reinforcing the concept of optimizing cancer treatments one patient at a time (n-of-1 approach). Additionally, our study used a novel artificial intelligence/machine learning (AI/ML) platform that leveraged drug responses and sequencing data to identify novel biomarkers of drug efficacy and gain potential mechanistic insights within specific subsets of pediatric cancer patients. The findings from our proof-of-principle study illustrate the impact of FPM for relapsed/refractory pediatric/adolescent cancer patients, highlight future integrations of FPM and AI/ML, and support ongoing patient cohort expansion (NCT05857969).

show abstract

Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology

Cited by 8 publications

References 49 publications

Metastatic Epithelioid Sarcoma of the Eyelid in a 47-Year-Old Man: A Case Report

Metastatic Epithelioid Sarcoma of the Eyelid in a 47-Year-Old Man: A Case Report

Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers

Functional Precision Medicine Enhances Clinical Outcomes of Relapsed/Refractory Pediatric and Adolescent Cancer Patients

Contact Info

Product

Resources

About