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

Nat Med. 2014 Jun;20(6):596-8. doi: 10.1038/nm.3548. Epub 2014 May 25.

Authors

Chen Liu¹, Rachid Karam², YingQi Zhou³, Fang Su⁴, Yuan Ji⁵, Gang Li⁶, GuoTong Xu⁷, LiXia Lu⁷, ChongRen Wang⁷, MeiYi Song⁷, JingPing Zhu⁷, YiRan Wang⁷, YiFan Zhao⁷, Wai Chin Foo⁸, MingXin Zuo⁹, Mark A Valasek¹⁰, Milind Javle⁹, Miles F Wilkinson¹¹, YanJun Lu⁷

Affiliations

¹ 1] Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. [2] Tongji University School of Life Science and Technology, Shanghai, China. [3].
² 1] Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA. [2].
³ 1] The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China. [2].
⁴ 1] Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. [2].
⁵ 1] Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. [2].
⁶ The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China.
⁷ Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
⁸ Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁹ Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁰ Division of Anatomic Pathology, Department of Pathology, University of California San Diego, San Diego, California, USA.
¹¹ 1] Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA. [2] Institute for Genomic Medicine, University of California San Diego, La Jolla, California, USA.

PMID: 24859531
PMCID: PMC4048332
DOI: 10.1038/nm.3548

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing / genetics*
Base Sequence
Carcinoma, Adenosquamous / genetics*
Gene Components
HEK293 Cells
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Molecular Sequence Data
Mutagenesis
Mutation / genetics
Nonsense Mediated mRNA Decay / genetics*
Pancreatic Neoplasms / genetics*
RNA Helicases
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Trans-Activators / genetics*

Substances

Trans-Activators
RNA Helicases
UPF1 protein, human

Associated data

GENBANK/KJ850256
GENBANK/KJ850257
GENBANK/KJ850258
GENBANK/KJ850259
GENBANK/KJ850260
GENBANK/KJ850261
GENBANK/KJ850262
GENBANK/KJ850263
GENBANK/KJ850264
GENBANK/KJ850265
GENBANK/KJ850266
GENBANK/KJ850267
GENBANK/KJ850268
GENBANK/KJ850269
GENBANK/KJ850270
GENBANK/KJ850271
GENBANK/KJ850272
GENBANK/KJ850273

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding