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The origins and consequences of UPF1 variants in pancreatic adenosquamous carcinoma

UID: 10794

Author(s): Polaski, Jacob T., Kannan, Ram*, Bradley, Robert K. * MSK affiliated

Description
Summary from the GEO: "Pancreatic adenosquamous carcinoma (PASC) is an aggressive cancer whose mutational origins are poorly understood. An early study reported high-frequency somatic mutations affecting UPF1, a core nonsense-mediated mRNA decay (NMD) factor, in PASC, but subsequent studies did not observe these lesions. The corresponding controversy about whether UPF1 mutations are important contributors to PASC has been exacerbated by a paucity of functional studies. Here, we modeled two UPF1 mutations to find no significant effects on pancreatic cancer growth, acquisition of adenosquamous features, UPF1 splicing, UPF1 protein levels, or NMD efficiency. We subsequently discovered that ~40% of UPF1 mutations reportedly present in PASCs are identical to standing genetic variants in the human population, suggesting that they may be non-pathogenic inherited variants rather than pathogenic mutations. Our data suggest that UPF1 is not a common functional driver of PASC and motivate further attempts to identify unique genetic features defining these malignancies."

Overall design from the GEO: "RNA-seq of HEK 293T cell lines carrying mutations in UPF1."
Subject of Study
Subject(s)
OncoTree Cancer Type(s)
Adenosquamous Carcinoma of the Pancreas
Access via GEO

XLSX files regarding expression profiling by high throughput sequencing
Accession #: GSE163517

Access via SRA

RNA sequencing of 9 samples.
Accession #: SRP298492

Access via BioProject

Additional information about the overall inititative.
Accession #: PRJNA686417

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2500
Software Used
SRA Toolkit
Dataset Format(s)
SRA, XLSX
Data Tool(s)
RNA Seq
Dataset Size
310.4 KB (XLSX). 14.3 Gb (SRA)
Data Catalog Record Updated
2023-12-07