Germline deletion of ETV6 in familial acute lymphoblastic leukemia

被引：22

作者：

Rampersaud, Evadnie ^{[1
]}

Ziegler, David S. ^{[2
,3
]}

Iacobucci, Ilaria ^{[4
]}

Payne-Turner, Debbie ^{[4
]}

Churchman, Michelle L. ^{[4
]}

Schrader, Kasmintan A. ^{[5
,6
]}

Joseph, Vijai ^{[7
,8
]}

Offit, Kenneth ^{[7
]}

Tucker, Katherine ^{[9
]}

Sutton, Rosemary ^{[3
]}

Warby, Meera ^{[9
,10
]}

Chenevix-Trench, Georgia ^{[11
]}

Huntsman, David G. ^{[5
,12
]}

Tsoli, Maria ^{[3
]}

Mead, R. Scott ^{[13
]}

Qu, Chunxu ^{[4
]}

Leventaki, Vasiliki ^{[4
]}

Wu, Gang ^{[1
]}

Mullighan, Charles G. ^{[4
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38112 USA

[2] Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW, Australia

[3] Univ New South Wales, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia

[4] St Jude Childrens Res Hosp, Dept Pathol, 262 Danny Thomas Pl,Mail Stop 342, Memphis, TN 38112 USA

[5] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada

[6] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[7] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[8] Sloan Kettering Inst, New York, NY USA

[9] Prince Wales Hosp, Hereditary Canc Ctr, Sydney, NSW, Australia

[10] Univ NSW Australia, Prince Wales Clin Sch, Sydney, NSW, Australia

[11] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia

[12] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[13] Prince Wales Hosp, South Eastern Area Lab Serv, Randwick, NSW, Australia

来源：

BLOOD ADVANCES | 2019年 / 3卷 / 07期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

GENETIC-VARIATION; STRUCTURAL-VARIATION; COPY-NUMBER; THROMBOCYTOPENIA; MUTATIONS; LANDSCAPE; RISK; TOOL; SET;

D O I：

10.1182/bloodadvances.2018030635

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent studies have identified germline mutations in TP53, PAX5, ETV6, and IKZF1 in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of ETV6 identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation. The ETV6 deletion was also identified by optimal structural variant analysis of exome sequencing data. These findings identify a new mechanism of germline predisposition in ALL and implicate ETV6 germline variation in predisposition to lymphoma. Importantly, these data highlight the importance of germline structural variant analysis in the search for germline variants predisposing to familial leukemia.

引用

页码：1039 / 1046

页数：8

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