Differences in Mutational Profile Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma Identified Using Next Generation Sequencing

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jun 29

PMID 31248021

Citations 17

Authors

Martyna Borowczyk

Ewelina Szczepanek-Parulska

Szymon Debicki

Bartlomiej Budny

Frederik A Verburg

Dorota Filipowicz

Barbara Wieckowska

Malgorzata Janicka-Jedynska

Lidia Gil

Katarzyna Ziemnicka

Marek Ruchala

Affiliations

Soon will be listed here.

Abstract

We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22-8.75)). The number of mutations was higher in patients with FTC than FTA (-value = 0.03). and mutations were present only in patients with FTA, while defects in , , , , , , and were detected exclusively in FTC patients. mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64-522.00); -value = 0.001. -positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; -value = 0.051). The presence of and with no mutations increased FTC detectability by 17.1%, whereas the absence of and with a presence of mutations increased FTA detectability by 5.7%. and are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of , , and mutations considered together.

Citing Articles

Routine Blood Tests as Predictive Tools for Differentiating Follicular Thyroid Carcinoma From Follicular Adenoma.

Wang J, Wang J, Liu H, Chen C Int J Gen Med. 2025; 18:733-744.

PMID: 39963518 PMC: 11830949. DOI: 10.2147/IJGM.S502626.

Diagnostic significance of ultrasound characteristics in discriminating follicular thyroid carcinoma from adenoma.

Xu R, Wen W, Zhang Y, Qian L, Liu Y BMC Med Imaging. 2024; 24(1):299.

PMID: 39501175 PMC: 11536847. DOI: 10.1186/s12880-024-01477-0.

Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment.

Borowczyk M, Kaczmarek-Rys M, Hryhorowicz S, Sypniewski M, Filipowicz D, Dobosz P J Endocrinol Invest. 2024; 47(12):2969-2980.

PMID: 38755492 PMC: 11549118. DOI: 10.1007/s40618-024-02389-0.

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression.

Zhou T, Ma N, Zhang Y, Chen X, Luo X, Zhang M Heliyon. 2024; 10(2):e23875.

PMID: 38293397 PMC: 10826616. DOI: 10.1016/j.heliyon.2023.e23875.

Metastatic follicular thyroid cancer with a longstanding responsiveness to gemcitabine plus oxaliplatin.

Dias D, Damasio I, Marques P, Simoes H, Rodrigues R, Cavaco B Eur Thyroid J. 2023; 12(3).

PMID: 36976625 PMC: 10235920. DOI: 10.1530/ETJ-22-0227.

References

Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry J, De Micco C . Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab. 2003; 88(6):2745-52. DOI: 10.1210/jc.2002-021186. View

Pencina M, DAgostino Sr R, DAgostino Jr R, Vasan R . Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2007; 27(2):157-72. DOI: 10.1002/sim.2929. View

Kumar P, Henikoff S, Ng P . Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009; 4(7):1073-81. DOI: 10.1038/nprot.2009.86. View

Kindler T, Lipka D, Fischer T . FLT3 as a therapeutic target in AML: still challenging after all these years. Blood. 2010; 116(24):5089-102. DOI: 10.1182/blood-2010-04-261867. View

McHenry C, Phitayakorn R . Follicular adenoma and carcinoma of the thyroid gland. Oncologist. 2011; 16(5):585-93. PMC: 3228182. DOI: 10.1634/theoncologist.2010-0405. View

Wiseman S, Griffith O, Gown A, Walker B, Jones S . Immunophenotyping of thyroid tumors identifies molecular markers altered during transformation of differentiated into anaplastic carcinoma. Am J Surg. 2011; 201(5):580-6. DOI: 10.1016/j.amjsurg.2011.01.010. View

Nikiforov Y, Nikiforova M . Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011; 7(10):569-80. DOI: 10.1038/nrendo.2011.142. View

Nikiforov Y, Ohori N, Hodak S, Carty S, LeBeau S, Ferris R . Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011; 96(11):3390-7. PMC: 3205883. DOI: 10.1210/jc.2011-1469. View

Krause K, Prawitt S, Eszlinger M, Ihling C, Sinz A, Schierle K . Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma. Am J Pathol. 2011; 179(6):3066-74. PMC: 3260833. DOI: 10.1016/j.ajpath.2011.08.033. View

10.

Karger S, Krause K, Engelhardt C, Weidinger C, Gimm O, Dralle H . Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours. J Mol Endocrinol. 2012; 48(3):193-202. DOI: 10.1530/JME-11-0119. View

11.

Smith C, Wang Q, Chin C, Salerno S, Damon L, Levis M . Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012; 485(7397):260-3. PMC: 3390926. DOI: 10.1038/nature11016. View

12.

Szczepanek-Parulska E, Zybek A, Biczysko M, Majewski P, Ruchala M . What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. Endokrynol Pol. 2012; 63(2):138-42. View

13.

Fukahori M, Yoshida A, Hayashi H, Yoshihara M, Matsukuma S, Sakuma Y . The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012; 22(7):683-9. DOI: 10.1089/thy.2011.0261. View

14.

Adzhubei I, Jordan D, Sunyaev S . Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013; Chapter 7:Unit7.20. PMC: 4480630. DOI: 10.1002/0471142905.hg0720s76. View

15.

Gupta N, Dasyam A, Carty S, Nikiforova M, Ohori N, Armstrong M . RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers. J Clin Endocrinol Metab. 2013; 98(5):E914-22. PMC: 5393462. DOI: 10.1210/jc.2012-3396. View

16.

Howell G, Hodak S, Yip L . RAS mutations in thyroid cancer. Oncologist. 2013; 18(8):926-32. PMC: 3755930. DOI: 10.1634/theoncologist.2013-0072. View

17.

Nikiforova M, Wald A, Roy S, Durso M, Nikiforov Y . Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013; 98(11):E1852-60. PMC: 3816258. DOI: 10.1210/jc.2013-2292. View

18.

Pfeifer A, Wojtas B, Oczko-Wojciechowska M, Kukulska A, Czarniecka A, Eszlinger M . Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues. BMC Med Genomics. 2013; 6:38. PMC: 3852913. DOI: 10.1186/1755-8794-6-38. View

19.

Pita J, Figueiredo I, Moura M, Leite V, Cavaco B . Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014; 99(3):E497-507. DOI: 10.1210/jc.2013-1512. View

20.

Schwarz J, Cooper D, Schuelke M, Seelow D . MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014; 11(4):361-2. DOI: 10.1038/nmeth.2890. View