Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact

In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n=30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13 center dot 11) and EYA2 (20q13 center dot 12). 210 (68 center dot 9%) patients had 'early MDS' without blast increase, 95 (31 center dot 1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28 center dot 9%) patients. Patients with advanced MDS more frequently had ACAs (P= 0 center dot 003) and had a higher mean number of ACAs (P=0 center dot 020) and of molecular mutations (P=0 center dot 060). Spliceosome mutations were frequent (U2AF1: n=31/155; 20 center dot 0%; SRSF2: n=31/159; 19 center dot 5%; SF3B1mut: n=8/159; 5 center dot 0%). ASXL1mut (25/153; 16 center dot 3%) were associated with advanced MDS (P=0 center dot 001). Presence of >= 3 ACAs (P=0 center dot 003) and ASXL1mut (P=0 center dot 002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse.