Age-related mutations associated with clonal hematopoietic expansion and malignancies.
Age-related mutations associated with clonal hematopoietic expansion and malignancies.
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作者：
在没有明显血液恶性肿瘤的个体的血液中检测到白血病和淋巴瘤的几种遗传改变特征。我们分析了癌症基因组图谱中2,728名个体的血液来源序列数据，发现了77种癌症相关基因的血液特异性突变，其中大多数与高龄相关。值得注意的是，这些突变中的83%来自19个白血病/淋巴瘤相关基因，其中9个是复发性突变（DNMT 3A，TET 2，JAK 2，ASXL 1，TP 53，GNAS，PPM 1D，BCORL 1和SF 3B 1）。我们在一小部分血细胞中发现了14个额外的突变，可能代表了造血干细胞克隆扩增的最早阶段。比较这些发现的突变在血液恶性肿瘤确定了几个复发突变的基因，可能是疾病的启动子。我们的分析表明，超过2%的个体（5%-6%的70岁以上的人）的血细胞含有可能代表癌前病变的突变，引发导致克隆造血扩增的事件。
Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion.
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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
骨髓增生性肿瘤中的体细胞CALR突变与未突破的JAK2。
DOI：
10.1056/nejmoa1312542
发表时间：
2013-12-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nangalia J;Massie CE;Baxter EJ;Nice FL;Gundem G;Wedge DC;Avezov E;Li J;Kollmann K;Kent DG;Aziz A;Godfrey AL;Hinton J;Martincorena I;Van Loo P;Jones AV;Guglielmelli P;Tarpey P;Harding HP;Fitzpatrick JD;Goudie CT;Ortmann CA;Loughran SJ;Raine K;Jones DR;Butler AP;Teague JW;O'Meara S;McLaren S;Bianchi M;Silber Y;Dimitropoulou D;Bloxham D;Mudie L;Maddison M;Robinson B;Keohane C;Maclean C;Hill K;Orchard K;Tauro S;Du MQ;Greaves M;Bowen D;Huntly BJP;Harrison CN;Cross NCP;Ron D;Vannucchi AM;Papaemmanuil E;Campbell PJ;Green AR
通讯作者：
Green AR
影响因子：
4.1
作者：
Pritchard, Colin C.;Salipante, Stephen J.;Walsh, Tom
通讯作者：
Walsh, Tom
影响因子：
10.5
作者：
Lu C;Venneti S;Akalin A;Fang F;Ward PS;Dematteo RG;Intlekofer AM;Chen C;Ye J;Hameed M;Nafa K;Agaram NP;Cross JR;Khanin R;Mason CE;Healey JH;Lowe SW;Schwartz GK;Melnick A;Thompson CB
通讯作者：
Thompson CB
影响因子：
30.8
作者：
Laurie, Cathy C.;Laurie, Cecelia A.;Rice, Kenneth;Doheny, Kimberly F.;Zelnick, Leila R.;McHugh, Caitlin P.;Ling, Hua;Hetrick, Kurt N.;Pugh, Elizabeth W.;Amos, Chris;Wei, Qingyi;Wang, Li-E;Lee, Jeffrey E.;Barnes, Kathleen C.;Hansel, Nadia N.;Mathias, Rasika;Daley, Denise;Beaty, Terri H.;Scott, Alan F.;Ruczinski, Ingo;Scharpf, Rob B.;Bierut, Laura J.;Hartz, Sarah M.;Landi, Maria Teresa;Freedman, Neal D.;Goldin, Lynn R.;Ginsburg, David;Li, Jun;Desch, Karl C.;Strom, Sara S.;Blot, William J.;Signorello, Lisa B.;Ingles, Sue A.;Chanock, Stephen J.;Berndt, Sonja I.;Le Marchand, Loic;Henderson, Brian E.;Monroe, Kristine R.;Heit, John A.;de Andrade, Mariza;Armasu, Sebastian M.;Regnier, Cynthia;Lowe, William L.;Hayes, M. Geoffrey;Marazita, Mary L.;Feingold, Eleanor;Murray, Jeffrey C.;Melbye, Mads;Feenstra, Bjarke;Kang, Jae H.;Wiggs, Janey L.;Jarvik, Gail P.;McDavid, Andrew N.;Seshan, Venkatraman E.;Mirel, Daniel B.;Crenshaw, Andrew;Sharopova, Nataliya;Wise, Anastasia;Shen, Jess;Crosslin, David R.;Levine, David M.;Zheng, Xiuwen;Udren, Jenna I.;Bennett, Siiri;Nelson, Sarah C.;Gogarten, Stephanie M.;Conomos, Matthew P.;Heagerty, Patrick;Manolio, Teri;Pasquale, Louis R.;Haiman, Christopher A.;Caporaso, Neil;Weir, Bruce S.
通讯作者：
Weir, Bruce S.