Somatic mutations precede myeloid leukemia years before diagnosis

被引：461

作者：

Desai, Pinkal ^{[1
]}

Mencia-Trinchant, Nuria ^{[1
]}

Savenkov, Oleksandr ^{[2
]}

Simon, Michael S. ^{[3
]}

Cheang, Gloria ^{[4
]}

Lee, Sangmin ^{[1
]}

Samuel, Michael ^{[1
]}

Ritchie, Ellen K. ^{[1
]}

Guzman, Monica L. ^{[1
]}

Ballman, Karla V. ^{[2
]}

Roboz, Gail J. ^{[1
]}

Hassane, Duane C. ^{[1
,5
,6
]}

机构：

[1] Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY 10065 USA

[2] Weill Cornell Med Coll, Heath Care Policy & Res, New York, NY USA

[3] Barbara Ann Karmanos Canc Inst, Detroit, MI USA

[4] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[5] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA

[6] Weill Cornell Med Coll, Caryl & Israel Englander Inst Precis Med, New York, NY 10065 USA

来源：

NATURE MEDICINE | 2018年 / 24卷 / 07期

基金：

美国国家卫生研究院;

关键词：

CLONAL HEMATOPOIESIS; EVOLUTION; COMMON;

D O I：

10.1038/s41591-018-0081-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The pattern of somatic mutations observed at diagnosis of acute myeloid leukemia (AML) has been well-characterized. However, the premalignant mutational landscape of AML and its impact on risk and time to diagnosis is unknown. Here we identified 212 women from the Women's Health Initiative who were healthy at study baseline, but eventually developed AML during follow-up (median time: 9.6 years). Deep sequencing was performed on peripheral blood DNA of these cases and compared to age-matched controls that did not develop AML. We discovered that mutations in IDH1, IDH2, TP53, DNMT3A, TET2 and spliceosome genes significantly increased the odds of developing AML. All subjects with TP53 mutations (n = 21 out of 21 patients) and IDH1 and IDH2 (n = 15 out of 15 patients) mutations eventually developed AML in our study. The presence of detectable mutations years before diagnosis suggests that there is a period of latency that precedes AML during which early detection, monitoring and interventional studies should be considered.

引用

页码：1015 / +

页数：10

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