Prognostic impact of somatic mutations and additional chromosomal abnormalities in patients with myelodysplastic syndromes and chromosome 20q deletion

The 20q deletion (del(20q)) is a recurrent chromosomal abnormality in individuals with myelodysplastic syndrome (MDS) and is associated with favourable outcomes when isolated. This study aims to analyse the clinical features and prognostic impact of del(20q) based on cytogenetic and molecular alterations. Among 1,527 patients with MDS, 101 (6.6%) exhibited del(20q): 67 (66.3%) had isolated del(20q), 16 (15.8%) had one additional chromosome abnormality (ACA), and 18 (17.8%) had ≥ 2 additional chromosome abnormalities (ACAs). Patients with ≥ 2 ACAs experienced shorter overall survival (OS) (12 months vs. 35 months vs. 24 months, respectively, p = 0.046) and leukaemia-free survival (LFS) (NR vs. NR vs. 22 months, respectively, p = 0.030), than those with one ACA or isolated del(20q). The del(20q) with ACAs subgroup had a higher incidence of ≥ 2 mutations and a greater median number of molecular mutations (p = 0.049 and p = 0.047, respectively). Interestingly, we found that multiple mutations within the same gene were present in 8.7% (6/69) of the analyzed samples. Notably, TET2 was the most frequently observed gene with multiple mutations, constituting 66.7% (4/6) of all cases. Furthermore, samples with TET2 mutations exhibited a significantly higher median number of mutations compared to those without TET2 mutations (3.0 [Interquartile Range [IQR], 1, 4] vs. 1.0[0, 2], p = 0.003). Patients with ≥ 2 mutations showed poorer OS and LFS (p < 0.001 and p = 0.007, respectively) compared to those with fewer mutations. The presence of multiple mutations (hazard ratio [HR] = 2.777, p = 0.049), U2AF1 mutations (HR = 3.595, p = 0.010), TET2 mutations (HR = 7.178, p = 0.002), and bone marrow blasts ≥ 10% (HR = 5.727, p = 0.002) were independently associated with poorer OS. In summary, del(20q) with ACAs is associated with more molecular abnormalities, increased risk of acute myeloid leukaemia transformation, and shorter OS than isolated del(20q). U2AF1 and TET2 mutations predict poor prognosis in patients with del(20q) MDS.