Steven Lehrer1, Peter H Rheinstein2. 1. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A. 2. Severn Health Solutions, Severna Park, MD, U.S.A.
Abstract
Background/Aim: It was recently shown that rare germline loss-of-function variants in the tyrosine-protein phosphatase non-receptor type 14 (PTPN14) gene conferred substantial risk of basal cell carcinoma (BCC). A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants were associated with high risk of cervical cancer and early age at diagnosis. We used the Cancer Genome Atlas (TCGA) to further evaluate the PTPN14 - cervical cancer association. Materials and Methods: We analyzed the Genomic Data Commons (GDC) TCGA Cervical Cancer (CESC) data set. We used cBioPortal for Cancer Genomics to access data in TCGA. cBioPortal provides visualization, analysis and download options for large-scale cancer genomic data sets. We also accessed TCGA data with the University of California Santa Cruz (UCSC) Xena Browser. UCSC Xena allows users to explore functional genomic data sets for assessing correlations between genomic and/or phenotypic variables. Results: Ten patients with PTPN14 mutations had significantly better survival than 266 patients without PTPN14 mutations (p=0.05 log rank test). In the Human Protein Atlas, low expression of PTPN14 in 85 TCGA cervical cancer specimens was associated with better survival than high expression in 206 cervical cancer specimens. Conclusion: In general, factors that affect the risk of a cancer have the same effect on prognosis. For example, history of allergy reduces risk of malignant brain tumors and improves prognosis. However, this relationship is not the case for PTPN14. We conclude that in TCGA cervical cancer specimens, PTPN14 mutation is a favorable prognostic factor. However, germline variants of PTPN14 confer a worse prognosis. Further studies of the specific mutations would be worthwhile. Copyright 2021, International Institute of Anticancer Research.
Background/Aim: It was recently shown that rare germline loss-of-function variants in the tyrosine-protein phosphatase non-receptor type 14 (PTPN14) gene conferred substantial risk of basal cell carcinoma (BCC). A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants were associated with high risk of cervical cancer and early age at diagnosis. We used the Cancer Genome Atlas (TCGA) to further evaluate the PTPN14 - cervical cancer association. Materials and Methods: We analyzed the Genomic Data Commons (GDC) TCGA Cervical Cancer (CESC) data set. We used cBioPortal for Cancer Genomics to access data in TCGA. cBioPortal provides visualization, analysis and download options for large-scale cancer genomic data sets. We also accessed TCGA data with the University of California Santa Cruz (UCSC) Xena Browser. UCSC Xena allows users to explore functional genomic data sets for assessing correlations between genomic and/or phenotypic variables. Results: Ten patients with PTPN14 mutations had significantly better survival than 266 patients without PTPN14 mutations (p=0.05 log rank test). In the Human Protein Atlas, low expression of PTPN14 in 85 TCGA cervical cancer specimens was associated with better survival than high expression in 206 cervical cancer specimens. Conclusion: In general, factors that affect the risk of a cancer have the same effect on prognosis. For example, history of allergy reduces risk of malignant brain tumors and improves prognosis. However, this relationship is not the case for PTPN14. We conclude that in TCGA cervical cancer specimens, PTPN14 mutation is a favorable prognostic factor. However, germline variants of PTPN14 confer a worse prognosis. Further studies of the specific mutations would be worthwhile. Copyright 2021, International Institute of Anticancer Research.
Entities:
Keywords:
The Cancer Genome Atlas; cervical cancer; genetics
Authors: Thorhildur Olafsdottir; Simon N Stacey; Gardar Sveinbjornsson; Gudmar Thorleifsson; Kristjan Norland; Bardur Sigurgeirsson; Kristin Thorisdottir; Arni Kjalar Kristjansson; Laufey Tryggvadottir; Kavita Y Sarin; Rafn Benediktsson; Jon G Jonasson; Asgeir Sigurdsson; Aslaug Jonasdottir; Snaedis Kristmundsdottir; Hakon Jonsson; Arnaldur Gylfason; Asmundur Oddsson; Run Fridriksdottir; Sigurjon A Gudjonsson; Florian Zink; Sigrun H Lund; Solvi Rognvaldsson; Pall Melsted; Valgerdur Steinthorsdottir; Julius Gudmundsson; Evgenia Mikaelsdottir; Pall I Olason; Lilja Stefansdottir; Hannes P Eggertsson; Bjarni V Halldorsson; Unnur Thorsteinsdottir; Tomas T Agustsson; Karl Olafsson; Jon H Olafsson; Patrick Sulem; Thorunn Rafnar; Daniel F Gudbjartsson; Kari Stefansson Journal: Cancer Res Date: 2021-02-18 Impact factor: 12.701