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.
authors.affiliation: 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].
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1] Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA. [2].
authors.forename: Rachid
authors.initials: R
authors.lastname: Karam
authors.affiliation: 1] The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China. [2].
authors.forename: YingQi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1] Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. [2].
authors.forename: Fang
authors.initials: F
authors.lastname: Su
authors.affiliation: 1] Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. [2].
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: The Third General Surgery Department, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: GuoTong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: LiXia
authors.initials: L
authors.lastname: Lu
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: ChongRen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: MeiYi
authors.initials: M
authors.lastname: Song
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: JingPing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: YiRan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: YiFan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Wai Chin
authors.initials: WC
authors.lastname: Foo
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: MingXin
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, University of California San Diego, San Diego, California, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Valasek
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.affiliation: 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.
authors.forename: Miles F
authors.initials: MF
authors.lastname: Wilkinson
authors.affiliation: Clinical and Translational Cancer Research Center, The Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: YanJun
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D018196:Carcinoma, Adenosquamous / Q000235:genetics*; D040461:Gene Components; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020365:RNA Helicases; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human