Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing.
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing.
复制标题
DOI：
10.1038/nature10738
复制
发表时间：
2012-01-11
期刊：
影响因子：
64.8
通讯作者：
DiPersio, John F.
中科院分区：
文献类型：
--
作者：
Ding, Li;Ley, Timothy J.;Larson, David E.;Miller, Christopher A.;Koboldt, Daniel C.;Welch, John S.;Ritchey, Julie K.;Young, Margaret A.;Lamprecht, Tamara;McLellan, Michael D.;McMichael, Joshua F.;Wallis, John W.;Lu, Charles;Shen, Dong;Harris, Christopher C.;Dooling, David J.;Fulton, Robert S.;Fulton, Lucinda L.;Chen, Ken;Schmidt, Heather;Kalicki-Veizer, Joelle;Magrini, Vincent J.;Cook, Lisa;McGrath, Sean D.;Vickery, Tammi L.;Wendl, Michael C.;Heath, Sharon;Watson, Mark A.;Link, Daniel C.;Tomasson, Michael H.;Shannon, William D.;Payton, Jacqueline E.;Kulkarni, Shashikant;Westervelt, Peter;Walter, Matthew J.;Graubert, Timothy A.;Mardis, Elaine R.;Wilson, Richard K.;DiPersio, John F.
大多数急性髓系白血病（AML）患者在复发后死于疾病进展，这与细胞遗传学水平的克隆进化有关。为了确定与复发相关的突变谱，我们对 8 名 AML 患者的原发肿瘤和复发基因组进行了测序，并使用深度测序验证了数百个体细胞突变；这使我们能够精确定义复发时的克隆性和克隆进化模式。除了在 AML 中发现新的、反复突变的基因（例如 WAC、SMC3、DIS3、DDX41 和 DAXX）之外，我们还发现了 AML 复发期间的两种主要克隆进化模式：1）原发肿瘤中的创始克隆获得突变并进化为复发克隆，或 2）创始克隆的亚克隆在初始治疗中存活下来，获得额外的突变并在复发时扩展。在所有情况下，化疗都未能根除创始克隆。所有 8 个病例中复发特异性突变与原发性肿瘤突变的比较显示颠换增加，可能是由于细胞毒性化疗引起的 DNA 损伤。这些数据表明，AML 复发与新突变和克隆进化的增加有关，这在一定程度上是由患者为建立和维持缓解而接受的化疗决定的。
Most patients with acute myeloid leukemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumor and relapse genomes from 8 AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to precisely define clonality and clonal evolution patterns at relapse. Besides discovering novel, recurrently mutated genes (e.g. WAC, SMC3, DIS3, DDX41, and DAXX) in AML, we found two major clonal evolution patterns during AML relapse: 1) the founding clone in the primary tumor gained mutations and evolved into the relapse clone, or 2) a subclone of the founding clone survived initial therapy, gained additional mutations, and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific vs. primary tumor mutations in all 8 cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped in part by the chemotherapy that the patients receive to establish and maintain remissions.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
影响因子：
64.8
作者：
Navin N;Kendall J;Troge J;Andrews P;Rodgers L;McIndoo J;Cook K;Stepansky A;Levy D;Esposito D;Muthuswamy L;Krasnitz A;McCombie WR;Hicks J;Wigler M
通讯作者：
Wigler M
DOI：
10.1073/pnas.88.11.4882
发表时间：
1991-06-01
影响因子：
11.1
作者：
GAO, JZ;ERICKSON, P;DRABKIN, HA
通讯作者：
DRABKIN, HA
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