Table 1

Methods for molecular monitoring of ctDNA for non-Hodgkin lymphoma

ctDNA of IgHctDNA of VDJ sequenceTumor genotypic ctDNA
Technique Allele-specific PCR PCR + NGS NGS 
Primary tumor required Yes No* No 
Sensitivity 1 in 105 1 in 106 Unknown 
Processing time Weeks 1-2 wk 1-2 wk 
Track clonal evolution No Limited Possible 
Track resistance No Limited Possible 
Potential Tumor-specific
Quantifiable 
Tumor-specific
Quantifiable
Universal primers
Rapid turnaround time 
Broad genomic coverage
Track clonal evolution
Track resistance mechanisms 
Limitations Not universal
Specific primers required
Limited foci assessed 
Limited genotypic information Low allele frequency
Molecular heterogeneity of tumor 
ctDNA of IgHctDNA of VDJ sequenceTumor genotypic ctDNA
Technique Allele-specific PCR PCR + NGS NGS 
Primary tumor required Yes No* No 
Sensitivity 1 in 105 1 in 106 Unknown 
Processing time Weeks 1-2 wk 1-2 wk 
Track clonal evolution No Limited Possible 
Track resistance No Limited Possible 
Potential Tumor-specific
Quantifiable 
Tumor-specific
Quantifiable
Universal primers
Rapid turnaround time 
Broad genomic coverage
Track clonal evolution
Track resistance mechanisms 
Limitations Not universal
Specific primers required
Limited foci assessed 
Limited genotypic information Low allele frequency
Molecular heterogeneity of tumor 

IgH, immunoglobulin heavy chain; NGS, next-generation sequencing; PCR, polymerase chain reaction; VDJ, variable-diversity-joining region of the immunoglobulin receptor.

*

Tumor clonotype can be determined without baseline tissue, but the yield is lower.

Mutational panels common to lymphoma subtypes would obviate the need for baseline tumor.

Sample size required to detect 1 cellular equivalent.

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