PTPN14 Mutations and Cervical Cancer
1Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.
2Severn Health Solutions, Severna Park, MD, U.S.A.
Abstract
In a recent study, Olafsdottir
Materials and Methods
We used cBioPortal for Cancer Genomics to analyze data in TCGA. cBioPortal provides visualization, analysis and download options of large-scale cancer genomics data sets (2). We also accessed TCGA data with the University of California Santa Cruz (UCSC) Xena Browser (https://xenabrowser.net) (3). UCSC Xena allows users to explore functional genomic data sets for assessing correlations between genomic and/or phenotypic variables. The UCSC Xena system was developed to enable cancer researchers to explore large public datasets. Xena hosts datasets from cancer genomics resources including TCGA, International Cancer Genome Consortium (ICGC) and the Genomic Data Commons (GDC). The system easily supports tens of thousands of samples and has been tested up to as many as a million cells. Using Xena we analyzed the GDC TCGA Cervical Cancer (CESC) data set.
Results
The age of cervical cancer patients was 48±14 years (mean±SD). Of the 276 cases of cervical cancer, 10 had PTPN14 mutations: 2 intron variants, one 5 prime UTR variant, 3 missense variants, 3 synonymous variants, and one stop gained variant. 7 of these mutations were identified in cBioPortal, which did not classify them as germline. The significance of these mutations is not known.
The 10 patients with PTPN14 mutations were significantly older (55±9 years) than the 266 patients without mutations (48±14 years,
The 10 patients with PTPN14 mutations had significantly better survival than 266 patients without PTPN14 mutations (
Discussion
The protein encoded by PTPN14 is a member of the protein tyrosine phosphatase (PTP) family and PTPN14 subfamily of tyrosine protein phosphatases. Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine phosphorylation is a common post-translational modification. In addition, PTPs are signalling molecules that regulate multiple cell processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. In cancer, PTPN14 interacts with and negatively regulates the oncogenic function of YAP, part of the Hippo signaling pathway determining cellular proliferation and survival (4).
In general, factors that affect the risk of a cancer have the same effect on prognosis. For example, history of allergy reduces the risk of malignant brain tumors and improves prognosis (5). However, this relationship does not hold in the case of PTPN14.
We conclude that in TCGA cervical cancer specimens, PTPN14 mutation is a favorable prognostic sign. However, germline variants of PTPN14 confer a worse prognosis, as reported by Olafsdottir
Conflicts of Interest
The Authors declare no conflicts of interest.
Authors’ Contributions
Dr. Lehrer and Dr. Rheinstein contributed equally to the conception and analyses in this study.
Acknowledgements
This work was supported, in part, through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was also supported by the Office of Research Infrastructure of the National Institutes of Health under award numbers S10OD018522 and S10OD026880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.