TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population.
Telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have recently been described in follicular cell-derived thyroid cancer (TC) in patients from North America and Europe. In this study, we explored whether these findings could be replicated in patients from a different ethnic group. We screened 17 benign thyroid adenomas and 265 TC samples from patients in the Middle East for these mutations by PCR and direct sequencing using DNA isolated from paraffin-embedded tumor tissues. None of the 17 benign adenomas harbored TERT promoter mutations. Of 265 TC, 34 (12.8%) harbored TERT promoter mutations, including 10/153 (6.5%) conventional papillary TC (CPTC), 8/57 (14.0%) follicular variant PTC, 9/30 (30%) tall cell variant PTC, 1/3 (30%) Hurthle cell thyroid cancer (HTC), 1/5 (20%) follicular TC, and 5/13 (38.5%) poorly differentiated TC. C250T mutation was present in only 6/265 (2.3%) cases, while C228T mutation was present in a total of 28/265 (10.6%) cases. These two mutations were mutually exclusive. TERT promoter mutations were significantly more common in older (≥45 years) than younger patients and were associated with larger tumour size, vascular invasion, higher TNM stage (stage III and IV), BRAF(V600E) mutation and persistent/recurrent disease at 6-12 months after initial treatment and at the last follow up. These associations were stronger in non-CPTC. Thus, this study on a large cohort of TC patients from Middle East demonstrates that TERT promoter mutations are relatively common, especially in the non-CPTC, and are associated with more aggressive histopathological features, BRAF(V600E) mutation, and disease persistence/recurrence than the WT TERT.
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ebtesam
E
Qasem
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Avaniyapuram Kannan
AK
Murugan
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hindi
H
Al-Hindi
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mingzhao
M
Xing
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mai
M
Almohanna
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Meshael
M
Alswailem
Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Molecular OncologyKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pathology and Laboratory MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of MedicineKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDivision of Endocrinology and MetabolismJohns Hopkins University School of Medicine, Baltimore, Maryland, USA aliz@kfshrc.edu.sa.
Ali S
AS
Alzahrani
D018263:Adenocarcinoma, Follicular / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000236:Adenoma / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D018249:Adenoma, Oxyphilic / Q000208:ethnology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D018912:Arabs / Q000235:genetics; D002291:Carcinoma, Papillary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002648:Child; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012008:Recurrence; D012529:Saudi Arabia / Q000453:epidemiology; D019098:Telomerase / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D013965:Thyroidectomy; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
carcinoma; thyroid