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Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia.

ABSTRACT: Circulating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing of ccfDNA and bone marrow at the time of diagnosis and after achieving remission in 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total of 39 unique somatic mutations were detected. Five mutations (13%) were detected only in ccfDNA, and 15 (38%) were detected only in bone marrow. Among the 19 mutations detected in both sources, the concordance of variant allelic frequency (VAF) assessment by both methods was high (R2 = 0.849). Mutations detected in only 1 source generally had lower VAF than those detected in both sources, suggesting that either method may miss small subclonal populations. In 3 patients, sequencing of ccfDNA detected new or persistent leukemia-associated mutations during remission that appeared to herald overt relapse. Overall, this study demonstrates that sequencing of ccfDNA in patients with AML can identify clinically relevant mutations not detected in the bone marrow and may play a role in the assessment of measurable residual disease. However, mutations were missed by both ccfDNA and bone marrow analyses, particularly when the VAF was <10%, suggesting that ccfDNA and bone marrow may be complementary in the assessment and monitoring of patients with AML.

SUBMITTER: Short NJ

PROVIDER: S-EPMC7189293 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia.

Short Nicholas J NJ Patel Keyur P KP Albitar Maher M Franquiz Miguel M Luthra Rajyalakshmi R Kanagal-Shamanna Rashmi R Wang Feng F Assi Rita R Montalban-Bravo Guillermo G Matthews Jairo J Ma Wanlong W Loghavi Sanam S Takahashi Koichi K Issa Ghayas C GC Kornblau Steven M SM Jabbour Elias E Garcia-Manero Guillermo G Kantarjian Hagop M HM Estrov Zeev Z Ravandi Farhad F

Blood advances 20200401 8

Circulating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing of ccfDNA and bone marrow at the time of diagnosis and after achieving remission in 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total of 39 unique somatic mutations were detected. Five mutations (13%) were detected only in cc ...[more]

PMID: 32324887

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Project description:BackgroundThe aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).MethodsBone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.ResultsAmong 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).ConclusionThis study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.

Dataset Information

Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia.

Publications

Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia.

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