Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis.
Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis.
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DOI：
10.1038/s41467-020-20565-7
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发表时间：
2021-01-12
影响因子：
16.6
通讯作者：
Papaemmanuil E
中科院分区：
文献类型：
--
作者：
Gao T;Ptashkin R;Bolton KL;Sirenko M;Fong C;Spitzer B;Menghrajani K;Ossa JEA;Zhou Y;Bernard E;Levine M;Martinez JSM;Zhang Y;Franch-Expósito S;Patel M;Braunstein LZ;Kelly D;Yabe M;Benayed R;Caltabellotta NM;Philip J;Paraiso E;Mantha S;Solit DB;Diaz LA Jr;Berger MF;Klimek V;Levine RL;Zehir A;Devlin SM;Papaemmanuil E
稳定获得的造血细胞突变代表了可能导致克隆性造血(CH)的选择底物，这是癌症患者的一种常见状态，与白血病发展的高风险有关。由于技术和样本量的限制，大多数CH研究都单独描述了基因突变或马赛克染色体改变(MCAS)。在这里，我们利用32,442名癌症患者的外周血测序数据来联合表征CH中的基因突变(n = 14,789)和MCA(n = 383)。在所有检测到的常染色体改变中，23%是与白血病基因组中已知的遗传交互作用相似的反复出现的复合基因型，这表明这些选择机制在克隆进化的早期起作用。具有复合基因型的CH定义了白血病进展的高危患者组(3年累积发病率14.6%，CI：7-22%)。多变量分析确定大脑中动脉是白血病发生的独立危险因素(HR = 14，95%CI：6-33，P <； 0.001)。我们的结果表明，在血液病风险患者的监测中，MCA应与基因突变一起考虑。实体癌患者克隆性造血率高，继发性白血病的风险增加。在这里，通过使用来自实体非血液性癌症患者的外周血测序数据，作者描绘了马赛克染色体改变和基因突变的图景，定义了白血病进展的高风险患者。
Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms. Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.
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影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
影响因子：
11.4
作者：
通讯作者：
--
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
DOI：
10.1126/science.aau3879
发表时间：
2018-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Martincorena I;Fowler JC;Wabik A;Lawson ARJ;Abascal F;Hall MWJ;Cagan A;Murai K;Mahbubani K;Stratton MR;Fitzgerald RC;Handford PA;Campbell PJ;Saeb-Parsy K;Jones PH
通讯作者：
Jones PH