Effect of single‐nucleotide polymorphism in TERT promoter on follicular thyroid tumor development

Abstract

Follicular thyroid neoplasm is a common tumor, and consists of follicular thyroid adenoma (FTA) and carcinoma (FTC). The mechanisms of tumor development of FTA and FTC are not well-understood. Single-nucleotide polymorphisms (SNPs) and point mutations in the telomerase reverse transcriptase (TERT) promoter have been associated with tumor development of many cancers. In order to clarify the significance of TERT promoter SNPs and mutations, including rs2853669 (−245T>C), C228T, and C250T, we analyzed 59 FTA patients and 19 FTC patients. Rs2853669 was found in 67.8% (40/59) and 57.9% (11/19) of FTAs and FTCs, respectively, and homozygous rs2853669 (CC) was more frequently found in FTC than in FTA. Furthermore, in FTA, rs2853669 was significantly associated with tumor size greater than 2.0 cm (P < 0.05).C228T was found in 5.1% and 36.8% of FTAs and FTCs, respectively. Frequencies of rs2853669 or/and C228T mutation were 71.2% in FTAs and 73.7%, in FTCs, and were significantly associated with larger tumor sizes in FTAs (P < 0.05). Rs2853669 is considered to be associated with tumor development in FTA and FTC.C228T, C250T, follicular thyroid adenoma, follicular thyroid carcinoma, follicular thyroid neoplasms, point mutation, rs2853669, single-nucleotide polymorphism, TERT promoter

Regulatory Single Nucleotide Polymorphism Increases <b><i>TERT</i></b> Promoter Activity in Thyroid Carcinoma Cells

“…rs2853669 has been detected in some malignant tumors, such as hepatocellular carcinomas [18], pulmonary carcinomas [16], glioblastoma [27], acute myeloid leukemia [17], and prostatic carcinomas [28]. Previous studies have shown that larger tumor sizes in PTCs and follicular thyroid tumors are influenced by rs2853669, and a greater influence has been observed for the combination of rs2853669 and C228T in PTCs [20,21]. Ko et al [18] reported that rs2853669 contributed to hepatocellular carcinoma progression by increasing TERT expression, and rs2853669 combined with the C228T mutation markedly increased TERT expression levels, resulting in poor overall and recurrence-free sur- vival rates among hepatocellular carcinoma patients [18].…”

“…A single nucleotide polymorphism (SNP), rs2853669 (-245T>C), has been reported in the TERT promoter [14,15], and associated with pulmonary carcinoma risk [16], shorter overall survival with acute myeloid leukemia [17], high mortality and recurrence rates with hepatocellular carcinoma [18], and low breast carcinoma risk [19]. The rs2853669 SNP has previously been reported to be associated with larger tumor size in PTC and follicular thyroid tumor cases in Japan [20,21]. A study has shown that the combination of rs2853669 and C228T is strongly associated with larger tumor size in patients with PTC [20].…”

<i>TERT</i> promoter mutations in thyroid cancer

“…There are inconsistencies even within the same type of cancer. In thyroid cancer, the coexistence of rs2853669 and the TERT-p mutation has been reported to be associated with an increase in tumor size [109,110]. Overall, however, the biological and clinical significance of rs2853669, especially in relation to TERT-p mutations, is still inconclusive, and further studies are definitely needed.…”

Spatial Distribution Patterns of Clinically Relevant TERT Promoter Mutations in Follicular Thyroid Tumors of Uncertain Malignant Potential

“…This specific mutational analysis seems to display excellent specificity, and a positive finding is therefore strongly linked to a thyroid malignancy. 16,20,41,42 At our institution, all FT-UMPs are routinely assessed for TERT promoter mutations postoperatively using conventional Sanger sequencing, and the finding of a mutation could mandate adjuvant treatment not otherwise offered to this patient category. 21 However, our current protocol dictates that DNA is extracted through cutting of formalin-fixated paraffin-embedded material from a single representative tissue block.…”