The origin and evolution of mutations in acute myeloid leukemia.
The origin and evolution of mutations in acute myeloid leukemia.
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DOI：
10.1016/j.cell.2012.06.023
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发表时间：
2012-07-20
期刊：
影响因子：
64.5
通讯作者：
Wilson RK
中科院分区：
文献类型：
--
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
癌症基因组中的大多数突变被认为是在起始事件后获得的，这可能会导致基因组不稳定，从而推动克隆进化。然而，对于急性髓系白血病（AML），正常核型很常见，基因组不稳定并不常见。为了更好地了解 AML 的克隆进化，我们对具有已知起始事件 (PML-RARA) 的 AML 样本与正常核型 AML 样本的基因组进行了测序，以及来自健康人的造血干/祖细胞 (HSPC) 的外显子组。总的来说，数据表明，AML 基因组中发现的大多数突变实际上是 HSPC 在获得起始突变之前发生的随机事件；随着克隆的扩展，该细胞的突变历史被“捕获”。在许多情况下，只需要一两个额外的协同突变即可产生恶性创始克隆。来自创始克隆的细胞可以获得额外的协同突变，产生可能导致疾病进展和/或复发的亚克隆。
Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability, driving clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of AML samples with a known initiating event (PML-RARA) vs. normal karyotype AML samples, and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is “captured” as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse.
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影响因子：
20.3
作者：
Abkowitz, JL;Golinelli, D;Guttorp, P
通讯作者：
Guttorp, P
肿瘤前期进展 人类干细胞群体的克隆进化
影响因子：
6
作者：
Calabrese, P;Tavaré, S;Shibata, D
通讯作者：
Shibata, D
影响因子：
20.3
作者：
Funk, Ryan K.;Maxwell, Taylor J.;Graubert, Timothy A.
通讯作者：
Graubert, Timothy A.
影响因子：
4.6
作者：
Betz, Bryan L.;Hess, Jay L.
通讯作者：
Hess, Jay L.
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