Landscape of genetic lesions in 944 patients with myelodysplastic syndromes.
Landscape of genetic lesions in 944 patients with myelodysplastic syndromes.
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作者：
高通量DNA测序显著有助于骨髓增生异常综合征(MDS)患者的诊断和预后。我们确定了遗传异常在MDS中的生物学和预后意义。总共有944名具有不同MDS亚型的患者被筛查104个基因的已知/可能的突变/缺失，使用靶向深度测序和基于阵列的基因组杂交。总体而言，845/944名患者(89.5%)至少有一个突变(中位数，每个患者3个；范围0-12)。47个基因发生显著突变，其中TET2、SF3B1、ASXL1、SRSF2、DNMT3A和RUNX1突变占10%。许多突变与高危人群和/或冲击波升高相关。对875例患者的生存情况进行了调查。通过单变量分析，25/48个基因(由47个显著检验的基因加上PRPF8产生)影响生存(P<；0.05)。14个基因结合常规因素的状态揭示了一个新的预后模型(模型-1)，该模型将患者分为低、中、高、极高四个风险组，3年生存率分别为95.2%、69.3%、32.8%和5.3%(P<；0.001)。随后，基于14个基因构建了一个“纯基因模型”(“模型-2”)，该模型也产生了四个显著的风险组(P<；0.001)。两种模型在验证队列中都是可重复的(n=175名患者；P<；各0.001例)。因此，大规模的多个靶基因的遗传和分子图谱对于MDS患者的亚型和预测是非常有价值的。
High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0–12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P<0.05). The status of 14 genes combined with conventional factors revealed a novel prognostic model (‘Model-1') separating patients into four risk groups (‘low', ‘intermediate', ‘high', ‘very high risk') with 3-year survival of 95.2, 69.3, 32.8, and 5.3% (P<0.001). Subsequently, a ‘gene-only model' (‘Model-2') was constructed based on 14 genes also yielding four significant risk groups (P<0.001). Both models were reproducible in the validation cohort (n=175 patients; P<0.001 each). Thus, large-scale genetic and molecular profiling of multiple target genes is invaluable for subclassification and prognostication in MDS patients.
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影响因子：
64.5
作者：
Welch JS;Ley TJ;Link DC;Miller CA;Larson DE;Koboldt DC;Wartman LD;Lamprecht TL;Liu F;Xia J;Kandoth C;Fulton RS;McLellan MD;Dooling DJ;Wallis JW;Chen K;Harris CC;Schmidt HK;Kalicki-Veizer JM;Lu C;Zhang Q;Lin L;O'Laughlin MD;McMichael JF;Delehaunty KD;Fulton LA;Magrini VJ;McGrath SD;Demeter RT;Vickery TL;Hundal J;Cook LL;Swift GW;Reed JP;Alldredge PA;Wylie TN;Walker JR;Watson MA;Heath SE;Shannon WD;Varghese N;Nagarajan R;Payton JE;Baty JD;Kulkarni S;Klco JM;Tomasson MH;Westervelt P;Walter MJ;Graubert TA;DiPersio JF;Ding L;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
6.1
作者：
DAVIDSON, R;MACKINNON, JG
通讯作者：
MACKINNON, JG
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J
DOI：
10.1056/nejmoa1013343
发表时间：
2011-06-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bejar R;Stevenson K;Abdel-Wahab O;Galili N;Nilsson B;Garcia-Manero G;Kantarjian H;Raza A;Levine RL;Neuberg D;Ebert BL
通讯作者：
Ebert BL