The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

Chen Liu; Rachid Karam; Yingqi Zhou; Fang Su; Yuan Ji; Gang Li; Guotong Xu; Lixia Lu; Chongren Wang; Meiyi Song; Jingping Zhu; Yiran Wang; Yifan Zhao; Wai Chin Foo; Mingxin Zuo; Mark A. Valasek; Milind Javle; Miles F. Wilkinson; Yanjun Lu

doi:10.1038/nm.3548

The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

Chen Liu, Rachid Karam, Yingqi Zhou, Fang Su, Yuan Ji, Gang Li, Guotong Xu, Lixia Lu, Chongren Wang, Meiyi Song, Jingping Zhu, Yiran Wang, Yifan Zhao, Wai Chin Foo, Mingxin Zuo, Mark A. Valasek, Milind Javle, Miles F. Wilkinson, Yanjun Lu

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102 Scopus citations

Abstract

Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.

Original language	English (US)
Pages (from-to)	596-598
Number of pages	3
Journal	Nature medicine
Volume	20
Issue number	6
DOIs	https://doi.org/10.1038/nm.3548
State	Published - Jun 2014

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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@article{f92b92fe619c480299f5bfb3ba630265,

title = "The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma",

abstract = "Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.",

author = "Chen Liu and Rachid Karam and Yingqi Zhou and Fang Su and Yuan Ji and Gang Li and Guotong Xu and Lixia Lu and Chongren Wang and Meiyi Song and Jingping Zhu and Yiran Wang and Yifan Zhao and Foo, {Wai Chin} and Mingxin Zuo and Valasek, {Mark A.} and Milind Javle and Wilkinson, {Miles F.} and Yanjun Lu",

note = "Funding Information: This work was supported by the National Key Basic Research Program of China grants 2013CB967500 and 2011DFB30010 (to G.X.) and 2011CB965102 (to L.L.), the National Natural Science Foundation of China grant 81071740 (to Y.J.) and a US National Institutes of Health grant (to M.F.W.). Vector pTBNde(mini)",

year = "2014",

month = jun,

doi = "10.1038/nm.3548",

language = "English (US)",

volume = "20",

pages = "596--598",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

AU - Liu, Chen

AU - Karam, Rachid

AU - Zhou, Yingqi

AU - Su, Fang

AU - Ji, Yuan

AU - Li, Gang

AU - Xu, Guotong

AU - Lu, Lixia

AU - Wang, Chongren

AU - Song, Meiyi

AU - Zhu, Jingping

AU - Wang, Yiran

AU - Zhao, Yifan

AU - Foo, Wai Chin

AU - Zuo, Mingxin

AU - Valasek, Mark A.

AU - Javle, Milind

AU - Wilkinson, Miles F.

AU - Lu, Yanjun

N1 - Funding Information: This work was supported by the National Key Basic Research Program of China grants 2013CB967500 and 2011DFB30010 (to G.X.) and 2011CB965102 (to L.L.), the National Natural Science Foundation of China grant 81071740 (to Y.J.) and a US National Institutes of Health grant (to M.F.W.). Vector pTBNde(mini)

PY - 2014/6

Y1 - 2014/6

N2 - Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.

AB - Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.

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JO - Nature medicine

JF - Nature medicine

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The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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