Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma

被引：110

作者：

Lee, Carolyn S. ^{[1
]}

Bhaduri, Aparna ^{[1
]}

Mah, Angela ^{[1
]}

Johnson, Whitney L. ^{[2
]}

Ungewickell, Alexander ^{[1
]}

Aros, Cody J. ^{[1
]}

Nguyen, Christie B. ^{[1
]}

Rios, Eon J. ^{[1
]}

Siprashvili, Zurab ^{[1
]}

Straight, Aaron ^{[2
]}

Kim, Jinah ^{[1
]}

Aasi, Sumaira Z. ^{[1
]}

Khavari, Paul A. ^{[1
,3
]}

机构：

[1] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA

[3] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA

来源：

NATURE GENETICS | 2014年 / 46卷 / 10期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

CANCER GENOME; SKIN-CANCER; ANEUPLOIDY; PATTERNS; P53;

D O I：

10.1038/ng.3091

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.

引用

页码：1060 / 1062

页数：3

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