Whole-exome sequencing identifies somatic ATRX mutations in pheochromocytomas and paragangliomas

被引：150

作者：

Fishbein, Lauren ^{[1
]}

Khare, Sanika ^{[2
]}

Wubbenhorst, Bradley ^{[2
]}

DeSloover, Daniel ^{[2
,3
]}

D'Andrea, Kurt ^{[2
]}

Merrill, Shana ^{[2
]}

Cho, Nam Woo ^{[4
]}

Greenberg, Roger A. ^{[4
,5
]}

Else, Tobias ^{[6
]}

Montone, Kathleen ^{[7
]}

LiVolsi, Virginia ^{[5
,7
]}

Fraker, Douglas ^{[5
,8
]}

Daber, Robert ^{[3
,7
]}

Cohen, Debbie L. ^{[9
]}

Nathanson, Katherine L. ^{[2
,5
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA

[3] Univ Penn, Ctr Personalized Diagnost, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA

[5] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[6] Univ Michigan Hlth Syst, Dept Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA

[7] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[8] Univ Penn, Perelman Sch Med, Dept Surg, Div Surg Oncol, Philadelphia, PA 19104 USA

[9] Univ Penn, Perelman Sch Med, Dept Med, Div Renal & Hypertens, Philadelphia, PA 19104 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

PROTOONCOGENE POINT MUTATIONS; RET PROTOONCOGENE; HISTONE CHAPERONE; SDH MUTATIONS; TUMORS; GENES; DAXX; ASSOCIATION; PHENOTYPE; SUCCINATE;

D O I：

10.1038/ncomms7140

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pheochromocytomas and paragangliomas (PCC/PGL) are the solid tumour type most commonly associated with an inherited susceptibility syndrome. However, very little is known about the somatic genetic changes leading to tumorigenesis or malignant transformation. Here we perform whole-exome sequencing on a discovery set of 21 PCC/PGL and identify somatic ATRX mutations in two SDHB-associated tumours. Targeted sequencing of a separate validation set of 103 PCC/PGL identifies somatic ATRX mutations in 12.6% of PCC/PGL. PCC/PGL with somatic ATRX mutations are associated with alternative lengthening of telomeres and clinically aggressive behaviour. This finding suggests that loss of ATRX, an SWI/SNF chromatin remodelling protein, is important in the development of clinically aggressive PCC/PGL.

引用

页数：6

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