Genetic profile of advanced thyroid cancers in relation to distant metastasis

in Endocrine-Related Cancer
Authors:
Eyun Song Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Eyun Song in
Current site
Google Scholar
PubMed Close
,
Dong Eun Song Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Dong Eun Song in
Current site
Google Scholar
PubMed Close
,
Jonghwa Ahn Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Jonghwa Ahn in
Current site
Google Scholar
PubMed Close
,
Tae Yong Kim Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Tae Yong Kim in
Current site
Google Scholar
PubMed Close
,
Won Bae Kim Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Won Bae Kim in
Current site
Google Scholar
PubMed Close
,
Young Kee Shong Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Young Kee Shong in
Current site
Google Scholar
PubMed Close
,
Min Ji Jeon Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Min Ji Jeon in
Current site
Google Scholar
PubMed Close
, and
Won Gu Kim Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Republic of Korea

Search for other papers by Won Gu Kim in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to M J Jeon or W G Kim: mj080332@gmail.com or wongukim@amc.seoul.kr
DOI:
https://doi.org/10.1530/ERC-19-0452
Volume/Issue:
Volume 27: Issue 5
Article Type:
Research Article
Page Range:
285–293
Online Publication Date:
May 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
Rent on DeepDyve

Sign up for journal news

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

Supplementary Materials

    • Supplementary Table 1. List of 50 target genes

Endocrine-Related Cancer is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 1339 74 0
PDF Downloads 986 48 0

 

  • Collapse
  • Expand
Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
9
Received Date:
30 Jan 2020
Accepted Date:
09 Mar 2020
Print Publication Date:
01 May 2020
Online Publication Date:
May 2020
Keywords:
genetic profile; next generation sequencing; advanced thyroid cancer; distant metastasis

  • Balmelli C, Railic N, Siano M, Feuerlein K, Cathomas R, Cristina V, Guthner C, Zimmermann S, Weidner S, Pless M, et al. 2018 Lenvatinib in advanced radioiodine-refractory thyroid cancer – a retrospective analysis of the Swiss lenvatinib named patient program. Journal of Cancer 9 250–255. (https://doi.org/10.7150/jca.22318)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Burns WR & Zeiger MA 2010 Differentiated thyroid cancer. Seminars in Oncology 37 557–566. (https://doi.org/10.1053/j.seminoncol.2010.10.008)

  • Cancer Genome Atlas Research Network 2014 Integrated genomic characterization of papillary thyroid carcinoma. Cell 159 676–690. (https://doi.org/10.1016/j.cell.2014.09.050)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, et al. 2006 Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. Journal of Clinical Endocrinology and Metabolism 91 2892–2899. (https://doi.org/10.1210/jc.2005-2838)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fukahori M, Yoshida A, Hayashi H, Yoshihara M, Matsukuma S, Sakuma Y, Koizume S, Okamoto N, Kondo T, Masuda M, et al. 2012 The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid 22 683–689. (https://doi.org/10.1089/thy.2011.0261)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Garcia-Rostan G, Zhao H, Camp RL, Pollan M, Herrero A, Pardo J, Wu R, Carcangiu ML, Costa J & Tallini G 2003 ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. Journal of Clinical Oncology 21 3226–3235. (https://doi.org/10.1200/JCO.2003.10.130)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Han JM, Bae JC, Kim HI, Kwon S, Jeon MJ, Kim WG, Kim TY, Shong YK & Kim WB 2018 Clinical outcomes of differentiated thyroid cancer patients with local recurrence or distant metastasis detected in old age. Endocrinology and Metabolism 33 459–465. (https://doi.org/10.3803/EnM.2018.33.4.459)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al. 2016 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 26 1–133. (https://doi.org/10.1089/thy.2015.0020)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hundahl SA, Fleming ID, Fremgen AM & Menck HR 1998 A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 83 2638–2648. (https://doi.org/10.1002/(sici)1097-0142(19981215)83:12<2638::aid-cncr31>3.0.co;2-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ibrahimpasic T, Ghossein R, Carlson DL, Nixon I, Palmer FL, Shaha AR, Patel SG, Tuttle RM, Shah JP & Ganly I 2014 Outcomes in patients with poorly differentiated thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 99 1245–1252. (https://doi.org/10.1210/jc.2013-3842)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ibrahimpasic T, Xu B, Landa I, Dogan S, Middha S, Seshan V, Deraje S, Carlson DL, Migliacci J, Knauf JA, et al. 2017 Genomic alterations in fatal forms of non-anaplastic thyroid cancer: identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence. Clinical Cancer Research 23 5970–5980. (https://doi.org/10.1158/1078-0432.CCR-17-1183)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jang EK, Song DE, Sim SY, Kwon H, Choi YM, Jeon MJ, Han JM, Kim WG, Kim TY, Shong YK, et al. 2014 NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. Thyroid 24 1275–1281. (https://doi.org/10.1089/thy.2014.0053)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jeon MJ, Chun SM, Lee JY, Choi KW, Kim D, Kim TY, Jang SJ, Kim WB, Shong YK, Song DE, et al. 2019 Mutational profile of papillary thyroid microcarcinoma with extensive lymph node metastasis. Endocrine 64 130–138. (https://doi.org/10.1007/s12020-019-01842-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ, Kim KW, Hahn SK, Youn YK, Kim KH, et al. 2012 The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer 118 1764–1773. (https://doi.org/10.1002/cncr.26500)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kim TY, Kim WG, Kim WB & Shong YK 2014 Current status and future perspectives in differentiated thyroid cancer. Endocrinology and Metabolism 29 217–225. (https://doi.org/10.3803/EnM.2014.29.3.217)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Landa I, Ganly I, Chan TA, Mitsutake N, Matsuse M, Ibrahimpasic T, Ghossein RA & Fagin JA 2013 Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. Journal of Clinical Endocrinology and Metabolism 98 E1562–E1566. (https://doi.org/10.1210/jc.2013-2383)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, Dogan S, Ricarte-Filho JC, Krishnamoorthy GP, Xu B, et al. 2016 Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. Journal of Clinical Investigation 126 1052–1066. (https://doi.org/10.1172/JCI85271)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li C, Lee KC, Schneider EB & Zeiger MA 2012 BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. Journal of Clinical Endocrinology and Metabolism 97 4559–4570. (https://doi.org/10.1210/jc.2012-2104)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu R & Xing M 2016 TERT promoter mutations in thyroid cancer. Endocrine-Related Cancer 23 R143–R155. (https://doi.org/10.1530/ERC-15-0533)

  • Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK & Xing M 2013 Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocrine-Related Cancer 20 603–610. (https://doi.org/10.1530/ERC-13-0210)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu C, Chen T & Liu Z 2016 Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World Journal of Surgical Oncology 14 241. (https://doi.org/10.1186/s12957-016-0979-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, et al. 2014 TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. Journal of Clinical Endocrinology and Metabolism 99 E754–E765. (https://doi.org/10.1210/jc.2013-3734)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Melo M, Gaspar da Rocha A, Batista R, Vinagre J, Martins MJ, Costa G, Ribeiro C, Carrilho F, Leite V, Lobo C, et al. 2017 TERT, BRAF, and NRAS in primary thyroid cancer and metastatic disease. Journal of Clinical Endocrinology and Metabolism 102 1898–1907. (https://doi.org/10.1210/jc.2016-2785)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nagaiah G, Hossain A, Mooney CJ, Parmentier J & Remick SC 2011 Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment. Journal of Oncology 2011 542358. (https://doi.org/10.1155/2011/542358)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Namba H, Rubin SA & Fagin JA 1990 Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Molecular Endocrinology 4 1474–1479. (https://doi.org/10.1210/mend-4-10-1474)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nikiforov YE 2008 Thyroid carcinoma: molecular pathways and therapeutic targets. Modern Pathology 21 (Supplement 2) S37–S43. (https://doi.org/10.1038/modpathol.2008.10)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Prior IA, Lewis PD & Mattos C 2012 A comprehensive survey of Ras mutations in cancer. Cancer Research 72 2457–2467. (https://doi.org/10.1158/0008-5472.CAN-11-2612)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qasem E, Murugan AK, Al-Hindi H, Xing M, Almohanna M, Alswailem M & Alzahrani AS 2015 TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population. Endocrine-Related Cancer 22 901–908. (https://doi.org/10.1530/ERC-15-0396)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Riesco-Eizaguirre G, Gutierrez-Martinez P, Garcia-Cabezas MA, Nistal M & Santisteban P 2006 The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I− targeting to the membrane. Endocrine-Related Cancer 13 257–269. (https://doi.org/10.1677/erc.1.01119)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Romei C, Ciampi R, Faviana P, Agate L, Molinaro E, Bottici V, Basolo F, Miccoli P, Pacini F, Pinchera A, et al. 2008 BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer. Endocrine-Related Cancer 15 511–520. (https://doi.org/10.1677/ERC-07-0130)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schlumberger MJ 1998 Papillary and follicular thyroid carcinoma. New England Journal of Medicine 338 297–306. (https://doi.org/10.1056/NEJM199801293380506)

  • Tavares C, Melo M, Cameselle-Teijeiro JM, Soares P & Sobrinho-Simoes M 2016 ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome. European Journal of Endocrinology 174 R117–R126. (https://doi.org/10.1530/EJE-15-0605)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vaisman F, Carvalho DP & Vaisman M 2015 A new appraisal of iodine refractory thyroid cancer. Endocrine-Related Cancer 22 R301–R310. (https://doi.org/10.1530/ERC-15-0300)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, et al. 2013 Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309 1493–1501. (https://doi.org/10.1001/jama.2013.3190)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yang X, Li J, Li X, Liang Z, Gao W, Liang J, Cheng S & Lin Y 2017 TERT promoter mutation predicts radioiodine-refractory character in distant metastatic differentiated thyroid cancer. Journal of Nuclear Medicine 58 258–265. (https://doi.org/10.2967/jnumed.116.180240)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Q, Liu SZ, Zhang Q, Guan YX, Chen QJ & Zhu QY 2016 Meta-analyses of association between BRAF(V600E) mutation and clinicopathological features of papillary thyroid carcinoma. Cellular Physiology and Biochemistry 38 763–776. (https://doi.org/10.1159/000443032)

    • PubMed
    • Search Google Scholar
    • Export Citation