Molecular Genetic Diagnostics in the Era of Genomic Medicine: Which method to choose to describe molecular profile of acute myeloid leukemia in children

Introduction: Acute myeloid leukemia (AML) is a genetically heterogeneous disease.Modern genetic Methodology: allow dividing AML into independent prognostically significant genetic subtypes, which are used to classify and stratify AML into risk groups. Methodology:To compare the sensitivity of targeted and whole-genome sequencing Methodology:, 50 random samples of pediatric AML were selected, diagnosed at the NRMC named after D.Rogachev in the laboratory of cytogenetics and molecular genetics at the onset of the disease.As part of the research protocol samples underwent targeted high-throughput sequencing (HTS) with the commercial kit (Qiagen, Germany) on the MiSeq (Illumina, USA) and as part of the national genetic initiative "100,000 genomes" whole-genome sequencing (WGS) was performed on the DNBSEQ-T7 platform (MGI, China) with MGIEasy FS PCR-Free DNA Library Prep Set (MGI, China).Results: Analysis of the myeloid panel revealed 135 variants with varying clinical significance.There were 1 to 6 variants per sample.The most frequently detected were in the FLT3, RAS pathway, and WT1 genes.The allelic frequency varied from 3 to 90% with an average coverage 1000x.Next we compared the variants detected in HTS with the variants detected in the same genomic regions by WGS.A total of 118 variants were identified, the average coverage per sample was 113x (28x to 248x).WGS detected 90% variants, which were detected by HTS with VAF >10%.