Consistency Analysis of Gene Mutation Sites of Bone Marrow Tumor DNA and Circulating Tumor DNA in Patients with Myelodysplastic Syndrome

OBJECTIVE: To analyze the consistency of gene mutation sites between bone marrow DNA (BM-tDNA) and perepheral plasma circulating tumor DNA (PP-ctDNA) in patients with myelodysplastic syndrome (MDS). METHODS: The simultaneous sampled BM and PP from 19 patients (SBPP) was detected by NGS-127 gene panel, and the consistency of VAF between BM-tDNA and PP-ctDNA was analyzed. The peripheral blood cell tumor DNA (PC-tDNA) of 5 out of 19 patients was detected randomly, the consistency of VAF among PC-tDNA，BM-tDNA and PP-ctDNA was analyzed. The non simultaneous sampled BM and PP from 13 patients (NBPP) was detected, and the difference value of VAF between BM-tDNA and PP-ctDNA in SBPP and NBPP was analyzed. RESULTS: The average concentration of PP-ctDNA in SBPP was 0.59 ng/µl and 0.604 ng/µl in NBPP. The median concentration of PP-ctDNA in SBPP and NBPP was 0.330 ng/µl and 0.338 ng/µl, respectively. The study showed a good consistency of VAF between BM-tDNA and PP-ctDNA in the SBPP (R2=0.9693, P<0.05), and the consistency of VAF between BM-tDNA and PP-ctDNA in single base replacement (SNP) sites (R2=0.9712) was better than that in insertion deletion (Indel) sites (R2=0.6813). The results showed a good consistency of VAF between BM-tDNA and PP-ctDNA both in 12 patients before treatment (R2=0.9325, P<0.05) and 5 patients (R2=0.9875, P<0.05) after treatment. The results also showed that the VAF of PC-tDNA had a good consistency with the VAF of BM-tDNA (R2=0.8783) and PP-ctDNA (R2=0.8783) (P<0.05). The difference value of VAF between BM-tDNA and PP-ctDNA in SBPP was significantly lower than that in NBPP (P<0.05). CONCLUSION: PP can replace BM as a biological sample for genes mutation detection in patients with MDS due to its stable concentration, high degree of consistency with bone marrow in clinical significant mutation sites and easy collection.