Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia - Experimental Hematology & Oncology

Tags

Top Highlights

• Many believed that the sequencing is gold standard method in diagnosis of mutation

• The recent advances of next-generation sequence (NGS) have made it more practical for clinical research to explore the cytogenetic analysis in many different diseases, including AML.

• In the last decade, significant progress has been made expanding the mutational landscape of AML [15,16,17], mainly due to advances in sequencing techniques.

• Unlike the Sanger unit time detection single segment, NGS can simultaneously detect signals of thousands of channels, thus greatly improving efficiency. More and more genetic mutations in MDS and AML patients have been detected and these mutations may serve as potential markers to extend the prognostic parameters in AML.

• 85.8% of AML patients had at least one mutation detected by targeted NGS

• older AML patients had significantly higher incidence of DNA methylation and hydroxymethylation-related genes, RNA spliceosome (14.0% vs 4.5%, p = 0.0064) gene mutations, and a trend of higher incidence of chromatin remodelling (28.1% vs 19.8%, p = 0.164) gene mutations

• TET2 had the highest gene mutation frequency (50.5%), followed by ASXL1 (19.1%), CEBPA (17.2%), FLT3–ITD (16.3%), DNMT3A (13.5%), NRAS (12.0%), NPM1 (11.1%), RUNX1 (7.7%) and IDH2 (6.8%) mutations

• frequency of molecular gene mutations at diagnosis was significantly higher in older patients than younger patients

• Older patients had significantly higher frequency of RUNX1, TP53, IDH 2 and SF3B1 gene mutations. Additionally, older patients also had a trend of higher frequency of ASXL1 gene mutations. However, there was no significant difference between younger and older groups for MDS patients.