Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis

被引：655

作者：

Busque, Lambert ^{[1
,2
]}

Patel, Jay P. ^{[4
]}

Figueroa, Maria E. ^{[5
]}

Vasanthakumar, Aparna ^{[6
]}

Provost, Sylvie ^{[3
]}

Hamilou, Zineb ^{[2
]}

Mollica, Luigina ^{[1
,2
]}

Li, Juan ^{[7
]}

Viale, Agnes ^{[7
]}

Heguy, Adriana ^{[4
]}

Hassimi, Maryam ^{[8
]}

Socci, Nicholas ^{[8
]}

Bhatt, Parva K. ^{[4
]}

Gonen, Mithat ^{[9
]}

Mason, Christopher E. ^{[10
,11
,12
]}

Melnick, Ari ^{[12
,13
]}

Godley, Lucy A. ^{[6
]}

Brennan, Cameron W. ^{[4
,14
]}

Abdel-Wahab, Omar ^{[4
,15
]}

Levine, Ross L. ^{[4
,12
,15
]}

机构：

[1] Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada

[2] Maisonneuve Rosemont Hosp, Dept Hematol, Montreal, PQ, Canada

[3] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada

[4] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[5] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[6] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA

[7] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10021 USA

[8] Mem Sloan Kettering Canc Ctr, Bioinformat Core, New York, NY 10021 USA

[9] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[10] Cornell Univ, Dept Physiol & Biophys, Weill Med Coll, New York, NY 10021 USA

[11] Cornell Univ, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, Weill Med Coll, New York, NY 10021 USA

[12] Cornell Univ, Weill Med Coll, Grad Sch Biomed Sci, New York, NY 10021 USA

[13] Cornell Univ, Weill Med Coll, Div Hematol Oncol, New York, NY 10021 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA

[15] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 11期

基金：

美国国家卫生研究院;

关键词：

STEM-CELLS; INACTIVATION PATTERNS; LEADS;

D O I：

10.1038/ng.2413

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aging is characterized by clonal expansion of myeloid-biased hematopoietic stem cells and by increased risk of myeloid malignancies. Exome sequencing of three elderly females with clonal hematopoiesis, demonstrated by X-inactivation analysis, identified somatic TET2 mutations. Recurrence testing identified TET2 mutations in 10 out of 182 individuals with X-inactivation skewing. TET2 mutations were specific to individuals with clonal hematopoiesis without hematological malignancies and were associated with alterations in DNA methylation.

引用

页码：1179 / 1181

页数：3

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