Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer

被引：277

作者：

Robinson, Dan R. ^{[1
,2
]}

Kalyana-Sundaram, Shanker ^{[1
,2
,3
]}

Wu, Yi-Mi ^{[1
,2
]}

Shankar, Sunita ^{[1
,2
]}

Cao, Xuhong ^{[1
,2
,4
]}

Ateeq, Bushra ^{[1
,2
]}

Asangani, Irfan A. ^{[1
,2
]}

Iyer, Matthew ^{[1
,5
]}

Maher, Christopher A. ^{[1
,2
,5
]}

Grasso, Catherine S. ^{[1
,2
]}

Lonigro, Robert J. ^{[1
,2
]}

Quist, Michael ^{[1
,2
]}

Siddiqui, Javed ^{[1
,2
]}

Mehra, Rohit ^{[1
,2
]}

Jing, Xiaojun ^{[1
,2
]}

Giordano, Thomas J. ^{[2
,6
]}

Sabel, Michael S. ^{[6
,7
]}

Kleer, Celina G. ^{[2
,6
]}

Palanisamy, Nallasivam ^{[1
,2
]}

Natrajan, Rachael ^{[8
]}

Lambros, Maryou B. ^{[8
]}

Reis-Filho, Jorge S. ^{[8
]}

Kumar-Sinha, Chandan ^{[1
,2
]}

Chinnaiyan, Arul M. ^{[1
,2
,4
,5
,6
,9
]}

机构：

[1] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

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

[3] Bharathidasan Univ, Dept Environm Biotechnol, Tiruchirappalli, Tamil Nadu, India

[4] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[7] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

[8] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[9] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA

来源：

NATURE MEDICINE | 2011年 / 17卷 / 12期

基金：

美国国家卫生研究院;

关键词：

FUSIONS; ACTIVATION; EXPRESSION;

D O I：

10.1038/nm.2580

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：

Breast cancer is a heterogeneous disease that has a wide range of molecular aberrations and clinical outcomes. Here we used paired-end transcriptome sequencing to explore the landscape of gene fusions in a panel of breast cancer cell lines and tissues. We observed that individual breast cancers have a variety of expressed gene fusions. We identified two classes of recurrent gene rearrangements involving genes encoding microtubule-associated serine-threonine kinase (MAST) and members of the Notch family. Both MAST and Notch-family gene fusions have substantial phenotypic effects in breast epithelial cells. Breast cancer cell lines harboring Notch gene rearrangements are uniquely sensitive to inhibition of Notch signaling, and overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo. These findings show that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions.

引用

页码：1646 / U163

页数：7

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