期刊
JOURNAL OF MOLECULAR DIAGNOSTICS
卷 23, 期 2, 页码 212-222出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmoldx.2020.10.016
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- Swedish Cancer Society
- Swedish Society for Medical Research
- Cancer Research Funds of Radiumhemmet
- Swedish Society of Medicine
- Lisa and Johan Gronberg Foundation
- Stockholm City Council
- Karolinska Institutet
Mutational heterogeneity of TERT promoter mutations was observed in most FT-UMPs, emphasizing the significance of tissue sampling process. The ddPCR technique may be more effective in detecting such mutations due to its increased sensitivity, suggesting potential for clinical screening purposes.
In thyroid carcinomas, telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T predict an unfavorable clinical outcome. The analysis is particularly valuable when assessing histologically equivocal follicular thyroid tumors of uncertain malignant potential (FT-UMPs). Given recent findings of TERT promoter mutational heterogeneity in thyroid cancer, we determined the frequency of this phenomenon in FT-UMPs and minimally invasive follicular thyroid carcinomas. DNA was extracted from several tissue blocks from 16 FT-UMPs as well as 10 minimally invasive follicular thyroid carcinomas, and interrogated using Sanger sequencing as well as digital droplet PCR (ddPCR). Mutational heterogeneity was observed by Sanger sequencing in four of seven (57%) FT-UMPs. In two FT-UMPs with C228T mutations, analyses of additional blocks gave wild-type results using Sanger sequencing in one or several blocks interrogated, whereas ddPCR found low-frequency C228T mutations in one of these fractions. In two additional FT-UMPs with the C228T and C250T mutation, respectively, sequencing of additional blocks revealed the opposite mutation. Moreover, in the C250T mutated area in one of these tumors, the ddPCR displayed a co-occurring C228T mutation that failed detection through Sanger sequencing. To conclude, most TERT promoter mutated FT-UMPs display mutational heterogeneity when analyzed by Sanger sequencing, thereby emphasizing the importance of the tissue sampling process. The ddPCR technique might overcome this phenomenon because of increased sensitivity and should be considered for clinical screening purposes.
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