Reliability of Cell-Free DNA and Targeted NGS in Predicting Chromosomal Abnormalities of Patients With Myeloid Neoplasms

Abstract

IntroductionCytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.MethodsPlasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.ResultsOf the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.ConclusionsThis data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.

Combining cell-free RNA with cell-free DNA in liquid biopsy for hematologic and solid tumors

“…4 C and D). The clinical utility of detecting chromosomal structural abnormalities using liquid biopsy and targeted gene DNA panel has been established [ 15 ]. Using large number of genes makes this detection more reliable.…”

“…The large panel of 1459 genes scattered throughout all chromosomes allows us to detect chromosomal structural abnormalities reliably in cfDNA. Th1459 gene panel covers significantly more genomic areas than our previous panel of 275 genes, which showed reliability in detecting chromosomal losses and gains [ 15 ].…”

Phase I Study of GS-3583, an FMS-like Tyrosine Kinase 3 Agonist Fc Fusion Protein, in Patients with Advanced Solid Tumors

“…NGS mutation analysis was performed at the Genomic Testing Cooperative according to a method described previously ( 29 ). In brief, genomic DNA was extracted from whole blood samples and sequencing was performed on an Illumina NextSeq 550 or a NovaSeq 6000 instrument.…”

Liquid biopsies and minimal residual disease in myeloid malignancies

“…cfDNA PB samples were taken. 54.5% of the patients showed the presence of mutations consistent with neoplastic clones in the circulation (72). Out of the 54.5%, 41% showed abnormalities associated with lymphoid neoplasms while 59% showed abnormalities associated with myeloid neoplasms.…”

“…In 89 AML or MDS patients stratified into intermediate, poor, or complex risk based on karyotype, there was a 100% concordance rate between cytologic and cfDNA specimens. Compared to BM samples, myeloid cfDNA using NGS samples accurately detected chromosomal gain and loss but were unable to diagnose fusion abnormalities (72). Giudice et al evaluated possible diagnostic and prognostic values of exosomal microRNAs in patients with AA and MDS.…”