Frequent somatic TERT promoter mutations in thyroid cancer: Higher prevalence in advanced ORMS of the disease Journal Article
| Authors: | Landa, I.; Ganly, I.; Chan, T. A.; Mitsutake, N.; Matsuse, M.; Ibrahimpasic, T.; Ghossein, R. A.; Fagin, J. A. |
| Article Title: | Frequent somatic TERT promoter mutations in thyroid cancer: Higher prevalence in advanced ORMS of the disease |
| Abstract: | Background: TERT encodes the reverse transcriptase component of telomerase, which adds telomere repeats to chromosome ends, thus enabling cell replication. Telomerase activity is required for cell immortalization. Somatic TERT promoter mutations modifying key transcriptional response elements were recently reported in several cancers, such as melanomas and gliomas. Objectives: The objectives of the study were: 1) to determine the prevalence of TERT promoter mutations C228T and C250T in different thyroid cancer histological types and cell lines; and 2) to establish the possible association of TERT mutations with mutations of BRAF, RAS, or RET/PTC. Methods: TERT promoter was PCR-amplified and sequenced in 42 thyroid cancer cell lines and 183 tumors: 80 papillary thyroid cancers (PTCs), 58 poorly differentiated thyroid cancers (PDTCs), 20 anaplastic thyroid cancers (ATCs), and 25 Hurthle cell cancers (HCCs). Results: TERT promoter mutationswerefound in 98 of 225 (44%) specimens. TERT promoters C228T and C250T were mutually exclusive. Mutations were present in 18 of 80 PTCs (22.5%), in 40 of 78 (51%) advanced thyroid cancers (ATC PDTC) (P 3 104 vs PTC), and in widely invasive HCCs (4 of 17), but not in minimally invasive HCCs (0 of 8). TERT promoter mutations were seen more frequently in advanced cancers with BRAF/RAS mutations compared to those that were BRAF/RAS wild-type (ATCPDTC, 67.3 vs 24.1%; P104), whereasBRAF-mutant PTCswereless likely to have TERT promoter mutations than BRAF wild-type tumors (11.8 vs 50.0%; P .04). Conclusions: TERT promoter mutations are highly prevalent in advanced thyroid cancers, particularly those harboring BRAF or RAS mutations, whereas PTCs with BRAF or RAS mutations are most often TERT promoter wild type. Acquisition of a TERT promoter mutation could extend survival of BRAF- or RAS-driven clones and enable accumulation of additional genetic defects leading to disease progression. Copyright © 2013 by The Endocrine Society. |
| Journal Title: | Journal of Clinical Endocrinology and Metabolism |
| Volume: | 98 |
| Issue: | 9 |
| ISSN: | 0021-972X |
| Publisher: | Oxford University Press |
| Date Published: | 2013-09-01 |
| Start Page: | E1562 |
| End Page: | E1566 |
| Language: | English |
| DOI: | 10.1210/jc.2013-2383 |
| PROVIDER: | scopus |
| PMCID: | PMC3763971 |
| PUBMED: | 23833040 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2013" - "CODEN: JCEMA" - "Source: Scopus" |
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180Fagin -
317Chan -
482Ghossein -
430Ganly -
16Ibrahimpasic -
19Landa-Lopez
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