title: TERT promoter mutations and long-term survival in patients with thyroid cancer.
abstract: TERT promoter mutations are emerging prognostic biomarkers in multiple cancers and are found in highly aggressive thyroid cancer. Our aim is to investigate the prognostic value of these mutations for the outcome of thyroid cancer-related mortality in a large cohort of thyroid cancer patients. This was a retrospective study of 409 patients (393 with differentiated thyroid cancer) with a median age of 44 years (range 16-81 years) and median follow-up of 13 years (interquartile range 11-16 years). Analyses of associations between mutational status and various clinicopathological variables were performed. TERT promoter mutations were identified in 32 (9.8%) papillary, 11 (16.7%) follicular and seven (43.8%) poorly differentiated/anaplastic thyroid cancer patients. The presence of TERT promoter mutations was associated with factors such as increased age (P < 0.001), extrathyroidal invasion (P = 0.01), increased stage at diagnosis (P < 0.001) and dedifferentiated histological type (P = 0.001). A TERT promoter mutation was independently associated with poorer overall survival in patients with differentiated thyroid cancer (10-year survival rate, 66.2% vs 98.3% for wild type; adjusted HR, 7.18; 95% CI: 2.77-18.59) and in patients with papillary cancer (74.2% vs 99.3%; 14.20; 3.03-66.68). Concomitant TERT and BRAF mutations worsened the survival rate of patients with papillary cancer (82.6% vs 99.4% for exclusively BRAF mutation alone; 5.62; 1.85-17.09). In conclusion, the presence of TERT promoter mutations is independently associated with increased mortality in patients with differentiated thyroid cancer. The results suggest that inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.
authors.affiliation: Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Tae Hyuk
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Green Cross GenomeYongin, Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of PathologySamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soomin
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Center for Clinical MedicineSamsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and GeneticsSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of PathologySamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Lyun
authors.initials: YL
authors.lastname: Oh
authors.affiliation: Biostatistics and Clinical Epidemiology CenterResearch Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyunga
authors.initials: K
authors.lastname: Kim
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, Seoul, Korea Department of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Samsung Genome InstituteSamsung Medical Center, Seoul, Korea Department of Molecular Cell BiologySungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choe
authors.affiliation: Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jee Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea thyroid@skku.edu.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF; TERT promoter; mortality; prognosis; thyroid cancer