When Tissue is an Issue the Liquid Biopsy is Nonissue: A Review.
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ABSTRACT:
SUBMITTER: Rodriguez J
PROVIDER: S-EPMC8140006 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.
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Project description:BackgroundLiquid biopsy (LB) is a promising complement to tissue biopsy for detection of clinically relevant genetic variants in cancer and mosaic diseases. A combined workflow to enable parallel tissue and LB analysis is required to maximize diagnostic yield for patients.MethodsWe developed and validated a cost-efficient combined next-generation sequencing (NGS) workflow for both tissue and LB samples, and applied Duplex sequencing technology for highly accurate detection of low frequency variants in plasma. Clinically relevant cutoffs for variant reporting and quantification were established.ResultsWe investigated assay performance characteristics for very low amounts of clinically relevant variants. In plasma, the assay achieved 100% sensitivity and 92.3% positive predictive value (PPV) for single nucleotide variants (SNVs) and 91.7% sensitivity and 100% PPV for insertions and deletions (InDel) in clinically relevant hotspots with 0.5-5% variant allele frequencies (VAFs). We further established a cutoff for reporting variants (i.e. Limit of Blank, LOB) at 0.25% VAF and a cutoff for quantification (i.e. Limit of Quantification, LOQ) at 5% VAF in plasma for accurate clinical interpretation of analysis results. With our LB approach, we were able to identify the molecular cause of a clinically confirmed asymmetric overgrowth syndrome in a 10-year old child that would have remained undetected with tissue analysis as well as other molecular diagnostic approaches.ConclusionOur flexible and cost-efficient workflow allows analysis of both tissue and LB samples and provides clinically relevant cutoffs for variant reporting and precise quantification. Complementing tissue analysis by LB is likely to increase diagnostic yield for patients with molecular diseases.
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