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Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
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Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.
Stefan K Alig1, Mohammad Shahrokh Esfahani1, Andrea Garofalo1
1Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA, USA.
Nature
|December 11, 2023
Summary
Liquid biopsies enable noninvasive genomic profiling of classic Hodgkin lymphoma (cHL). This study identifies two cHL subtypes and a targetable IL4R mutation, improving risk prediction and minimal residual disease detection.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Classic Hodgkin lymphoma (cHL) presents challenges for genomic analysis due to scarce malignant cells in tissue.
- Liquid biopsies, using circulating tumor DNA (ctDNA), offer a promising alternative for molecular profiling in cHL.
Purpose of the Study:
- To investigate the utility of liquid biopsies for comprehensive genomic profiling of cHL.
- To identify distinct genomic subtypes and therapeutic targets in cHL.
- To assess the role of ctDNA in risk prediction and minimal residual disease detection.
Main Methods:
- Analysis of plasma ctDNA from 366 cHL patients.
- Leveraging single-cell transcriptional profiles to understand ctDNA shedding.
- Utilizing PhasED-seq for longitudinal ctDNA monitoring.
Main Results:
- Plasma ctDNA mutation representation exceeds bulk tumor representation in most cHL cases.
- Identified two distinct cHL genomic subtypes with unique clinical, transcriptional, and immunological features.
- Discovered IL4R mutations targetable with IL-4Rα-blocking antibodies.
- Demonstrated ctDNA levels effectively refine risk prediction and detect minimal residual disease.
Conclusions:
- Noninvasive strategies are valuable for genotyping and dynamic monitoring of cHL.
- Identification of molecularly distinct subtypes offers diagnostic, prognostic, and therapeutic potential.
- Liquid biopsies represent a powerful tool for advancing cHL management.
