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Blood Plasma Methylated DNA Markers in the Detection of Lymphoma: Discovery, Validation, and Clinical Pilot

  • 0Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
American Journal of Hematology +

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November 20, 2024

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November 20, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Methylated DNA markers (MDMs) in plasma show promise for detecting lymphoma, achieving 78% sensitivity. These markers could aid in early cancer detection and multi-cancer screening efforts.

Area Of Science

  • Oncology
  • Molecular Diagnostics
  • Genomics

Background

  • Lymphoma is a significant cause of cancer mortality, yet lacks effective population screening methods.
  • The potential of methylated DNA markers (MDMs) for lymphoma detection remains underexplored.
  • Tissue-derived MDMs offer a promising avenue for developing non-invasive diagnostic tools.

Purpose Of The Study

  • To discover, validate, and test tissue-derived MDMs for lymphoma detection in plasma specimens.
  • To establish the diagnostic accuracy of these MDMs in a clinical setting.
  • To evaluate the potential of plasma MDMs for inclusion in multi-cancer screening panels.

Main Methods

  • Reduced representation bisulfite sequencing (RRBS) was used for MDM discovery in frozen tissues.
  • Methylation-specific PCR assays were developed and validated on formalin-fixed, paraffin-embedded (FFPE) tissues.
  • Target enrichment long-probe quantitative-amplified signal (TELQAS) assays were used to analyze plasma DNA from lymphoma patients and healthy controls, with random forest modeling for prediction.

Main Results

  • Sixteen specific MDM assays (e.g., ZNF503, HOXA9, TPBG) were selected for plasma testing.
  • The assays detected 78% of lymphoma cases with 90% specificity.
  • Sensitivity increased to 84% when excluding marginal zone and T-cell lymphomas.

Conclusions

  • Plasma-based MDMs demonstrate significant potential for lymphoma detection.
  • These markers are viable candidates for further investigation in multi-cancer early detection studies.
  • The findings support the development of non-invasive blood tests for lymphoma screening.

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