title: BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients.
abstract: The role of telomerase reverse transcriptase (TERT) gene promoter mutations in the aggressiveness of papillary thyroid cancer (PTC) remains to be further investigated. Here we examined the relationship of TERT promoter mutations and BRAF V600E with the clinicopathological features of PTC in 653 patients. Sanger sequencing of genomic DNA from primary PTC tumors was performed for mutation detection and genotype-clinicopathological correlation of the tumor was analyzed. BRAF V600E and TERT promoter mutations were found in 63.7% (416 of 653) and 4.1% (27 of 653) of patients, respectively; the latter became 9.8% when only tumors ≥ 1.5 cm were analyzed. TERT promoter mutations occurred more frequently in BRAF mutation-positive cases compared to wild-type cases, being 5.3% in the former versus 2.1% in the latter (P = 0.050). BRAF and TERT promoter mutations were each significantly associated with high-risk clinicopathological features of PTC, such as old patient age, large tumor size, extrathyroidal invasion, capsular invasion, and advanced disease stages. Coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, as exemplified by extrathyroidal invasion seen in 54.5% (12/22) of patients harboring both mutations versus 9.9% (23/232) of patients harboring neither mutation (P < 0.001). Thus, this study, the largest on TERT mutation so far, demonstrates a significant role of BRAF V600E and TERT promoter mutations in the aggressiveness of PTC, which is particularly robust and cooperative when the two mutations coexist. These results, together with previous studies, establish a significant role of these mutations in the aggressiveness of PTC.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Langping
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Endong
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Ruichao
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Chuanmeng
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Yehuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgical Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Wu
authors.affiliation: Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Ouchen
authors.initials: O
authors.lastname: Wang
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF V600E mutation; TERT promoter mutation; molecular marker; papillary thyroid carcinoma; prognosis