title: Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact.
abstract: 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; 29-90 years). 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 (20q13·11) and EYA2 (20q13·12). 210 (68·9%) patients had 'early MDS' without blast increase, 95 (31·1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28·9%) patients. Patients with advanced MDS more frequently had ACAs (P = 0·003) and had a higher mean number of ACAs (P = 0·020) and of molecular mutations (P = 0·060). Spliceosome mutations were frequent (U2AF1: n = 31/155; 20·0%; SRSF2: n = 31/159; 19·5%; SF3B1mut: n = 8/159; 5·0%). ASXL1mut (25/153; 16·3%) were associated with advanced MDS (P = 0·001). Presence of ≥3 ACAs (P = 0·003) and ASXL1mut (P = 0·002) 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.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Melanie
authors.initials: M
authors.lastname: Zenger
authors.forename: Manja
authors.initials: M
authors.lastname: Meggendorfer
authors.forename: Sabine
authors.initials: S
authors.lastname: Jeromin
authors.forename: Andreas
authors.initials: A
authors.lastname: Roller
authors.forename: Vera
authors.initials: V
authors.lastname: Grossmann
authors.forename: Maria-Theresa
authors.initials: MT
authors.lastname: Krauth
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20; D003582:Cytogenetics; D005260:Female; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
keywords: 20q deletion; SRSF2 mutation; U2AF1 mutation; cytogenetics; myelodysplastic syndromes