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Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact
Author(s) -
Bacher Ulrike,
Haferlach Torsten,
Schnittger Susanne,
Zenger Melanie,
Meggendorfer Manja,
Jeromin Sabine,
Roller Andreas,
Grossmann Vera,
Krauth MariaTheresa,
Alpermann Tamara,
Kern Wolfgang,
Haferlach Claudia
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12710
Subject(s) - myelodysplastic syndromes , cytogenetics , comparative genomic hybridization , fluorescence in situ hybridization , medicine , biology , international prognostic scoring system , monosomy , chromosome , karyotype , genetics , bone marrow , gene
Summary 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%; SF3B1 mut: n = 8/159; 5·0%). ASXL1 mut (25/153; 16·3%) were associated with advanced MDS ( P = 0·001). Presence of ≥3 ACAs ( P = 0·003) and ASXL1 mut ( 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. U2AF1 mut is overrepresented in MDS with del(20q), and ASXL1 mut is prognostically adverse.