Journal article
Germline POT1 Variants in a Pan-Cancer Cohort
JCO precision oncology, Vol.9, e2400946
07/2025
DOI: 10.1200/PO-24-00946
PMCID: PMC12243956
PMID: 40632976
Abstract
Purpose
Germline likely pathogenic and pathogenic variants (LPV/PVs) in POT1 have been associated with an increased risk of various cancers including angiosarcoma, melanoma, glioma, thyroid cancer, and chronic lymphocytic leukemia (CLL). However, to date, most of the published data regarding POT1 PVs involve cohorts of patients selected for specific cancer types, or stem from commercial laboratory cohorts from patients selected for germline clinical testing, which may cause ascertainment biases. The objective was to identify germline POT1 variants in a pan-cancer cohort and describe the associated phenotypes.
Methods
Germline exome data available for 19,315 patients with cancer from the Oncology Research Information Exchange Network (ORIEN) were assessed for POT1 LPV/PV. Data regarding cancer diagnoses were obtained for those with and without POT1 variants. Associations were assessed.
Results
POT1 LPV/PVs were identified in 23 patients. The cancer types seen in more than one patient include CLL (n = 7), papillary thyroid cancer (PTC, n = 5), colorectal cancer (n = 3), lung cancer (n = 3), glioblastoma (n = 2), and neuroendocrine tumors (n = 2). Compared with POT1-negative patients, those with POT1 LPV/PVs were 5.5-fold more likely to be diagnosed with PTC (95% CI, 1.9 to 15.1; P = .004) and 16.6-fold more likely to be diagnosed with CLL (95% CI, 6.4 to 41.9; P < .001). Patients with POT1 LPV/PVs had a younger median age of first cancer diagnosis compared with POT1-negative patients (P = .008).
Conclusion
To our knowledge, this study is the largest investigation of POT1 germline variants in a pan-cancer cohort. We identify and confirm specific associations with CLL and PTC in this cohort. Differences in results between analysis of largely unselected cohorts compared with clinical testing cohorts highlight the need to study gene-cancer associations in more unselected populations.
Details
- Title: Subtitle
- Germline POT1 Variants in a Pan-Cancer Cohort
- Creators
- Pamela L Brock - The Ohio State UniversityMorgan Webster - Legacy HealthSandya Liyanarachchi - The Ohio State UniversityLindsey Byrne - The Ohio State UniversityDale J HedgesPat Gulhati - Rutgers, The State University of New JerseyJ Kevin Hicks - Moffitt Cancer CenterCarlos H F Chan - University of Iowa Health CareKenan Onel - Roswell Park Comprehensive Cancer CenterLeigh Anne Stout - Indiana University – Purdue University IndianapolisWhitney Maxwell - Huntsman Cancer Institute, University of Utah, Salt Lake City, UTJustine Cooper Pickarski - Markey Cancer CenterJuvianee Estrada-Veras - Uniformed Services University of the Health SciencesBodour Salhia - University of Southern CaliforniaLisen Axell - University of Colorado Anschutz Medical CampusLaura L Holman - University of Oklahoma Health Sciences CenterMohamed H Abdel-Rahman - The Ohio State UniversityMatthew D Ringel - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- JCO precision oncology, Vol.9, e2400946
- DOI
- 10.1200/PO-24-00946
- PMID
- 40632976
- PMCID
- PMC12243956
- NLM abbreviation
- JCO Precis Oncol
- ISSN
- 2473-4284
- eISSN
- 2473-4284
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- P30 CA016058 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 07/2025
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984845451002771
Metrics
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