MLL Munich Leukemia Laboratory, Munich, Germany.
Br J Haematol. 2014 Mar;164(6):822-33. doi: 10.1111/bjh.12710. Epub 2013 Dec 26.
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.
在骨髓增生异常综合征（MDS）患者中，单纯 20q 缺失[del(20q)]是一种常见的有利异常。我们研究了 305 例 del(20q)的 MDS 患者中其他分子和细胞遗传学病变及其预后影响，其中 229 例为男性/76 例为女性；年龄 29-90 岁。所有患者均通过细胞形态学和染色体带分析（CBA）进行检查，亚组患者通过荧光原位杂交、分子突变筛查和阵列比较基因组杂交（aCGH）进行检查。通过 aCGH（n = 30），最小常见缺失区域（CDR）由 PTPRT（20q13·11）和 EYA2（20q13·12）两侧包围。210 例（68.9%）患者为无白血病增多的“早期 MDS”，95 例（31.1%）为有白血病增多的“晚期 MDS”（5-19%）。在 305 例患者中有 88 例（28.9%）存在其他染色体异常（ACAs）。晚期 MDS 患者更常发生 ACAs（P = 0.003），并且平均 ACAs 数量更多（P = 0.020）和分子突变数量更多（P = 0.060）。剪接体突变很常见（U2AF1：n = 31/155；20.0%；SRSF2：n = 31/159；19.5%；SF3B1mut：n = 8/159；5.0%）。ASXL1mut（n = 153；16.3%）与晚期 MDS 相关（P = 0.001）。存在≥3 个 ACAs（P = 0.003）和 ASXL1mut（P = 0.002）与较差的 2 年生存率相关。总之，del(20q)的 MDS 细胞遗传学亚组具有良好的预后，但可通过额外的细胞遗传学和分子病变进一步细分。U2AF1mut 在 del(20q)的 MDS 中过度表达，ASXL1mut 预后不良。
