Circulating tumor DNA in Hodgkin lymphoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Somatic mutations in key signaling pathways (NF-κB, PI3K/AKT, NOTCH, JAK/STAT) are crucial in Hodgkin lymphoma (HL) pathogenesis.
• Despite comprising only ~5% of tumor mass, HL tumor DNA is detectable in blood as circulating tumor DNA (ctDNA).

Purpose of the Study:

• To review advancements in ctDNA analysis for Hodgkin lymphoma.
• To highlight ctDNA's role in genetic profiling, clonal evolution, and prognostic assessment.
• To explore ctDNA's potential in guiding biomarker-driven therapy and monitoring treatment response.

Main Methods:

• Analysis of ctDNA for qualitative and quantitative detection of tumor-specific somatic mutations.
• Review of ctDNA detection methodologies and their application in HL.
• Correlation of ctDNA levels with patient prognosis and treatment outcomes.

Main Results:

• STAT6 is the most frequently mutated gene in HL, with mutation spectrum varying by histological subtype.
• ctDNA reflects the genetic landscape of HL tumor cells, enabling liquid biopsy.
• A reduction in ctDNA plasma levels post-treatment strongly correlates with favorable prognosis.

Conclusions:

• ctDNA analysis is a promising non-invasive tool for Hodgkin lymphoma.
• ctDNA facilitates comprehensive tumor genome analysis, aiding in personalized medicine.
• ctDNA serves as a powerful method for minimal residual disease monitoring and detecting treatment resistance.