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Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation.
Diagn Pathol 2016; 11:21DP

Abstract

BACKGROUND

Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations.

METHODS

We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers.

RESULTS

TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025).

CONCLUSIONS

The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations.

Authors+Show Affiliations

Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. drbae@catholic.ac.kr.Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. chuchura@naver.com. Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. chuchura@naver.com.Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. thfk38@nate.com. Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. thfk38@nate.com.Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. smilie21@naver.com.Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. kimecho@catholic.ac.kr.Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. leesohee@catholic.ac.kr.Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. benedict@catholic.ac.kr.Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. ldj6026@catholic.ac.kr.Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. lys9908@catholic.ac.kr.Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. ckjung@catholic.ac.kr.

Pub Type(s)

Evaluation Studies
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26857243

Citation

Bae, Ja Seong, et al. "Clinical Utility of TERT Promoter Mutations and ALK Rearrangement in Thyroid Cancer Patients With a High Prevalence of the BRAF V600E Mutation." Diagnostic Pathology, vol. 11, 2016, p. 21.
Bae JS, Kim Y, Jeon S, et al. Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagn Pathol. 2016;11:21.
Bae, J. S., Kim, Y., Jeon, S., Kim, S. H., Kim, T. J., Lee, S., ... Jung, C. K. (2016). Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagnostic Pathology, 11, p. 21. doi:10.1186/s13000-016-0458-6.
Bae JS, et al. Clinical Utility of TERT Promoter Mutations and ALK Rearrangement in Thyroid Cancer Patients With a High Prevalence of the BRAF V600E Mutation. Diagn Pathol. 2016 Feb 9;11:21. PubMed PMID: 26857243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. AU - Bae,Ja Seong, AU - Kim,Yourha, AU - Jeon,Sora, AU - Kim,Se Hee, AU - Kim,Tae Jung, AU - Lee,Sohee, AU - Kim,Min-Hee, AU - Lim,Dong Jun, AU - Lee,Youn Soo, AU - Jung,Chan Kwon, Y1 - 2016/02/09/ PY - 2015/09/05/received PY - 2016/01/14/accepted PY - 2016/2/10/entrez PY - 2016/2/10/pubmed PY - 2016/10/13/medline SP - 21 EP - 21 JF - Diagnostic pathology JO - Diagn Pathol VL - 11 N2 - BACKGROUND: Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations. METHODS: We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers. RESULTS: TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025). CONCLUSIONS: The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations. SN - 1746-1596 UR - https://www.unboundmedicine.com/medline/citation/26857243/Clinical_utility_of_TERT_promoter_mutations_and_ALK_rearrangement_in_thyroid_cancer_patients_with_a_high_prevalence_of_the_BRAF_V600E_mutation_ L2 - https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-016-0458-6 DB - PRIME DP - Unbound Medicine ER -