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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.

SUBMITTER: Liu C

PROVIDER: S-EPMC4048332 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Liu Chen C Karam Rachid R Zhou YingQi Y Su Fang F Ji Yuan Y Li Gang G Xu GuoTong G Lu LiXia L Wang ChongRen C Song MeiYi M Zhu JingPing J Wang YiRan Y Zhao YiFan Y Foo Wai Chin WC Zuo MingXin M Valasek Mark A MA Javle Milind M Wilkinson Miles F MF Lu YanJun Y

Nature medicine 20140525 6

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, ...[more]

PMID: 24859531

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The origins and consequences of <i>UPF1</i> variants in pancreatic adenosquamous carcinoma.

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