Abstract
BACKGROUND: Isolated 20q deletion [del(20q)] is a recurrent favorable abnormality in myelodysplastic syndrome (MDS) and may cause deletion of the ASXL1 gene. Meanwhile, ASXL1 mutations are also common in individuals with MDS. This study aimed to describe the biological and clinical implications of ASXL1 mutations and deletion in newly diagnosed MDS patients with isolated del(20q). METHODS: Gene mutation and copy number alterations in 178 newly diagnosed MDS patients with isolated del(20q) were analyzed using DNA next generation sequencing. RESULTS: Twenty-five (14%) of 178 patients were found to have ASXL1 mutations, which exhibited lower absolute neutrophil counts (ANC) (p = 0.006), a higher percentage of bone marrow blasts (p = 0.001), more mutant genes (p < 0.001), higher IPSS-R (p = 0.038) and IPSS-M (p = 0.001) risk groups. Furthermore, ASXL1 mutations were preferentially associated with mutations in U2AF1, and most ASXL1 mutations (68%) were observed as subclonal lesions. ASXL1 frameshift mutations were associated with a worse prognosis in MDS patients with low blasts (MDS-LB) (p = 0.043), but not in those with increased blasts (MDS-IB). Twenty-two (26.8%) of 82 patients were found to have ASXL1 deletion, which exhibited a lower IPSS-M risk group, lower platelet counts, higher ANC levels, and higher hemoglobin levels compared to ASXL1 patients(only-mut) and ASXL1(wt) patients. Two (2.4%) of the 82 patients exhibited biallelic ASXL1 inactivation (ASXL1(mut&del)). CONCLUSIONS: ASXL1 mutations are one of the late genetic events in MDS patients with isolated 20q deletion, and different types of ASXL1 gene alterations have distinct clinical and biological characteristics.