Abstract 1141: Telomerase activity in relation to RET mutation status in medullary thyroid carcinoma
2012
Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL
Background: Medullary thyroid carcinoma (MTC) originates from parafollicular C cells of the thyroid gland, and are associated with activating constitutional or somatic mutations in the RET proto-oncogene. The common somatic mutation of codon 918 is associated with a less favorable clinical outcome. The catalytic component of telomerase, human telomerase reverse transcriptase (TERT) has been found to be reactivated in most human tumors. Objective: In this study, we aimed to investigate telomerase involvement in relation the RET mutational status in MTC. Design: Our study includes 43 cases of MTC from the Karolinska University Hospital. RET mutations were identified by sequencing of the hot spots in exons 10,\_11-,\_15-, and 16. Expression of the TERT gene, telomerase activity and telomere length were quantified. Result: Among the 43 cases, 18 carried a RET point mutation in exon15 or exon16 (Group I), 5/43 had a point mutation in exon 10 or 11 (Group II), and 20 were wild-type (Group III). Telomerase activity and TERT expression were closely associated. The TERT gene was expressed in 13/18 cases in Group I, in 0/5 in Group II and in 10/20 of Group III. The median telomerase activity was higher in Group I as compared to Groups II and III. Group I tumors showed the shortest relative telomere length. With regard to follow-up, cases with high telomerase activity and TERT gene expression in Group I had less favorable outcome. Conclusion: The findings suggest that TERT/telomerase activity may contribute to aggressive MTC in addition to, or as a consequence of, RET codon 918 mutations. The very low telomerase activity and TERT expression revealed in several of the MTC cases suggest the involvement of alternative mechanisms for telomere stabilization in the MTC entity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1141. doi:1538-7445.AM2012-1141
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