白血病中的精准基因组学揭示南亚患者的突变与融合图谱以指导临床决策

Background: The integration of next-generation sequencing (NGS) into routine diagnostic workflows is revolutionizing molecular characterization in cancer care, enabling precise detection of pathogenic variants and other fusion transcripts. Particularly in malignant haematological diseases, NGS has significantly enhanced diagnostic accuracy and prognostic assessment, providing critical insights that directly inform and optimize clinical decision making. To support precision oncology in routine clinical practice, various in-house developed and commercial NGS based leukemia panels have been adopted. In this study, leukemic patient samples from an Indian cohort were analysed to identify the most statistically significant gene mutations and chromosomal fusions implicated in leukemic disorders. Methods: Genomic profiling, including fusion detection, was performed on 98 leukemic samples using the G2M Hemat NGS assay, which targets 208 clinically relevant genes including DNA fusion and 94 RNA fusion genes and approximately 650 kb of genomic regions and was sequenced on the Illumina platform. Bioinformatics analysis was conducted using the GATK v4.1.2 somatic variant calling pipeline, and downstream visualization of mutational landscapes and hotspot regions was achieved using MAF tools. Results: Comprehensive genomic profiling revealed recurrent mutations in ASXL1, FLT3, PTPN11, NRAS, KRAS, BCOR, ABL1, NF1, KIT, and EZH2, with variant allele frequencies ranging from 2% to 16%, emphasizing their potential role in leukemogenesis. Additionally, seven clinically significant RNA fusion genes were identified across 19 patient samples, with RUNX1-RUNX1T1 and ETV6-RUNX1 emerging as the most prevalent, followed by the hallmark BCR-ABL1 fusion. Key substitutions including Gly→Val (ASXL1), Asp→Tyr (FLT3) at specified position, and multiple changes in signalling genes define a clinically relevant spectrum of amino acid changes in leukemia. These findings highlight a complex mutational and fusion landscape with critical implications for risk profiling and targeted therapy development. Conclusion: The ability to detect clinically relevant mutations and fusion genes that inform diagnosis, prognostic stratification, and precision treatment decisions in hematologic malignancies, establishes the assay's value as a comprehensive genomic tool for precision oncology.