TY - JOUR
T1 - TERT promoter mutations in thyroid cancer
T2 - A report from a Middle Eastern population
AU - Qasem, Ebtesam
AU - Murugan, Avaniyapuram Kannan
AU - Al-Hindi, Hindi
AU - Xing, Mingzhao
AU - Almohanna, Mai
AU - Alswailem, Meshael
AU - Alzahrani, Ali S.
N1 - Publisher Copyright:
© 2015 Society for Endocrinology.
PY - 2015/12
Y1 - 2015/12
N2 - 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), BRAFV600E 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, BRAFV600E mutation, and disease persistence/recurrence than the WT TERT.
AB - 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), BRAFV600E 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, BRAFV600E mutation, and disease persistence/recurrence than the WT TERT.
KW - Carcinoma
KW - Thyroid
UR - http://www.scopus.com/inward/record.url?scp=84948142133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948142133&partnerID=8YFLogxK
U2 - 10.1530/ERC-15-0396
DO - 10.1530/ERC-15-0396
M3 - Article
C2 - 26354077
AN - SCOPUS:84948142133
SN - 1351-0088
VL - 22
SP - 901
EP - 908
JO - Endocrine-related cancer
JF - Endocrine-related cancer
IS - 6
ER -