Advertisement

Genomic Applications in Thyroid Cancer

  • Thomas J. Giordano
Chapter

Abstract

The last decade has witnessed the characterization of the cancer genome through the harmonized application of next-generation genomic technologies by large research networks such as The Cancer Genome Atlas. Thyroid cancer, especially the most common types derived from follicular thyroid cells, has been included in such genomic efforts. In this chapter, the oncogenic genetic and genomic alterations across the spectrum of thyroid cancers are presented, as well as the resulting genomic clinical applications in molecular pathology. In the current era of precision oncology, these genomic advances are yielding critical insights into thyroid cancer pathogenesis and facilitating the development of novel diagnostic molecular tools.

Keywords

Cancer Carcinoma Endocrine Pathology Thyroid Genetics Genome Mutation Papillary Follicular Anaplastic 

References

  1. 1.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefGoogle Scholar
  2. 2.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C. Ten years of next-generation sequencing technology. Trends Genet. 2014;30(9):418–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Blum A, Wang P, Zenklusen JC. SnapShot: TCGA-analyzed tumors. Cell. 2018;173(2):530.PubMedCrossRefGoogle Scholar
  5. 5.
    Giordano TJ. Genomic hallmarks of thyroid neoplasia. Annu Rev Pathol. 2018;13:141–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676–90.CrossRefGoogle Scholar
  7. 7.
    Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A, et al. Comprehensive characterization of cancer driver genes and mutations. Cell. 2018;173(2):371–85.e18.PubMedCrossRefGoogle Scholar
  8. 8.
    Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet. 2015;24(8):2318–29.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Karunamurthy A, Panebianco F, Hsiao S J, Vorhauer J, Nikiforova MN, Chiosea S, et al. Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocr Relat Cancer. 2016;23(4):295–301.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016;126(3):1052–66.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Yoo SK, Lee S, Kim SJ, Jee HG, Kim BA, Cho H, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet. 2016;12(8):e1006239.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Martin-Marcos P, Zhou F, Karunasiri C, Zhang F, Dong J, Nanda J, et al. eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast. elife. 2017;6Google Scholar
  13. 13.
    Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014;505(7484):495–501.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Wreesmann VB, Ghossein RA, Hezel M, Banerjee D, Shaha AR, Tuttle RM, et al. Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity. Genes Chromosomes Cancer. 2004;40(4):355–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, et al. Genomic and functional approaches to understanding cancer aneuploidy. Cancer Cell. 2018;33(4):676–89. e3PubMedCrossRefGoogle Scholar
  16. 16.
    Vandin F, Clay P, Upfal E, Raphael BJ. Discovery of mutated subnetworks associated with clinical data in cancer. Pac Symp Biocomput. 2012:55–66.Google Scholar
  17. 17.
    Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017;45(D1):D777–D83.PubMedCrossRefGoogle Scholar
  18. 18.
    Eszlinger M, Krohn K, Hauptmann S, Dralle H, Giordano TJ, Paschke R. Perspectives for improved and more accurate classification of thyroid epithelial tumors. J Clin Endocrinol Metab. 2008;93(9):3286–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Wylie D, Beaudenon-Huibregtse S, Haynes BC, Giordano TJ, Labourier E. Molecular classification of thyroid lesions by combined testing for miRNA gene expression and somatic gene alterations. J Pathol Clin Res. 2016;2(2):93–103.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Fagin JA, Wells SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375(11):1054–67.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Kidger AM, Keyse SM. The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs). Semin Cell Dev Biol. 2016;50:125–32.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Afkhami M, Karunamurthy A, Chiosea S, Nikiforova MN, Seethala R, Nikiforov YE, et al. Histopathologic and clinical characterization of thyroid tumors carrying the BRAF(K601E) mutation. Thyroid. 2016;26(2):242–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Pozdeyev N, Gay L, Sokol ES, Hartmaier RJ, Deaver KE, Davis SN, et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin Cancer Res. 2018;24:3059.PubMedCrossRefGoogle Scholar
  25. 25.
    Cheng DT, Mitchell TN, Zehir A, Shah RH, Benayed R, Syed A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17(3):251–64.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31(11):1023–31.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Prasad ML, Vyas M, Horne MJ, Virk RK, Morotti R, Liu Z, et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in Northeast United States. Cancer. 2016;122(7):1097–107.PubMedCrossRefGoogle Scholar
  28. 28.
    Hardee S, Prasad ML, Hui P, Dinauer CA, Morotti RA. Pathologic characteristics, natural history, and prognostic implications of BRAF(V600E) mutation in pediatric papillary thyroid carcinoma. Pediatr Dev Pathol. 2017;20(3):206–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Vanden Borre P, Schrock AB, Anderson PM, Morris JC 3rd, Heilmann AM, Holmes O, et al. Pediatric, adolescent, and young adult thyroid carcinoma harbors frequent and diverse targetable genomic alterations, including kinase fusions. Oncologist. 2017;22(3):255–63.CrossRefGoogle Scholar
  30. 30.
    Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, et al. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. 2018;173(2):291–304. e6PubMedCrossRefGoogle Scholar
  31. 31.
    Ding L, Bailey MH, Porta-Pardo E, Thorsson V, Colaprico A, Bertrand D, et al. Perspective on oncogenic processes at the end of the beginning of cancer genomics. Cell. 2018;173(2):305–20. e10PubMedCrossRefGoogle Scholar
  32. 32.
    Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. The immune landscape of cancer. Immunity. 2018;48(4):812–30. e14PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic signaling pathways in the cancer genome atlas. Cell. 2018;173(2):321–37. e10PubMedCrossRefGoogle Scholar
  34. 34.
    Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318–26.PubMedCrossRefGoogle Scholar
  35. 35.
    Harach HR, Soubeyran I, Brown A, Bonneau D, Longy M. Thyroid pathologic findings in patients with Cowden disease. Ann Diagn Pathol. 1999;3(6):331–40.PubMedCrossRefGoogle Scholar
  36. 36.
    Swierniak M, Pfeifer A, Stokowy T, Rusinek D, Chekan M, Lange D, et al. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing. Mol Cell Endocrinol. 2016;433:130–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Jung SH, Kim MS, Jung CK, Park HC, Kim SY, Liu J, et al. Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma. Oncotarget. 2016;7(43):69638–48.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hemmer S, Wasenius VM, Knuutila S, Joensuu H, Franssila K. Comparison of benign and malignant follicular thyroid tumours by comparative genomic hybridization. Br J Cancer. 1998;78(8):1012–7.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Roque L, Rodrigues R, Pinto A, Moura-Nunes V, Soares J. Chromosome imbalances in thyroid follicular neoplasms: a comparison between follicular adenomas and carcinomas. Genes Chromosomes Cancer. 2003;36(3):292–302.PubMedCrossRefGoogle Scholar
  40. 40.
    Garcia-Rendueles ME, Ricarte-Filho JC, Untch BR, Landa I, Knauf JA, Voza F, et al. NF2 loss promotes oncogenic RAS-induced thyroid cancers via YAP-dependent transactivation of RAS proteins and sensitizes them to MEK inhibition. Cancer Discov. 2015;5(11):1178–93.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014;33(42):4978–84.PubMedCrossRefGoogle Scholar
  42. 42.
    Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99(5):E754–65.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kim TH, Kim YE, Ahn S, Kim JY, Ki CS, Oh YL, et al. TERT promoter mutations and long-term survival in patients with thyroid cancer. Endocr Relat Cancer. 2016;23(10):813–23.PubMedCrossRefGoogle Scholar
  44. 44.
    Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016;23(3):R143–55.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Song J, Yang Z. Case report: whole exome sequencing of circulating cell-free tumor DNA in a follicular thyroid carcinoma patient with lung and bone metastases. J Circ Biomark. 2018;7:1849454418763725.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Carcangiu ML. Hurthle cell carcinoma: clinic-pathological and biological aspects. Tumori. 2003;89(5):529–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Satoh M, Yagawa K. Electron microscopic study on mitochondria in Hurthle cell adenoma of thyroid. Acta Pathol Jpn. 1981;31(6):1079–87.PubMedGoogle Scholar
  48. 48.
    Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, Iommarini L, et al. Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A. 2007;104(21):9001–6.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Evangelisti C, de Biase D, Kurelac I, Ceccarelli C, Prokisch H, Meitinger T, et al. A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors. BMC Cancer. 2015;15:157.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LG, Liang Y, et al. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab. 2013;98(5):E962–72.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Corver WE, Ruano D, Weijers K, den Hartog WC, van Nieuwenhuizen MP, de Miranda N, et al. Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma. PLoS One. 2012;7(6):e38287.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Xu B, Ghossein R. Genomic landscape of poorly differentiated and anaplastic thyroid carcinoma. Endocr Pathol. 2016;27(3):205–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Volante M, Rapa I, Gandhi M, Bussolati G, Giachino D, Papotti M, et al. RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab. 2009;94(12):4735–41.PubMedCrossRefGoogle Scholar
  54. 54.
    Pita JM, Figueiredo IF, Moura MM, Leite V, Cavaco BM. 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.PubMedCrossRefGoogle Scholar
  55. 55.
    Hiltzik D, Carlson DL, Tuttle RM, Chuai S, Ishill N, Shaha A, et al. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients. Cancer. 2006;106(6):1286–95.PubMedCrossRefGoogle Scholar
  56. 56.
    Bonhomme B, Godbert Y, Perot G, Al Ghuzlan A, Bardet S, Belleannee G, et al. Molecular pathology of anaplastic thyroid carcinomas: a retrospective study of 144 cases. Thyroid. 2017;27(5):682–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017;170(6):1062–78.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Eischen CM. Genome stability requires p53. Cold Spring Harb Perspect Med. 2016;6(6):pii: a026096.CrossRefGoogle Scholar
  59. 59.
    Tomasini R, Mak TW, Melino G. The impact of p53 and p73 on aneuploidy and cancer. Trends Cell Biol. 2008;18(5):244–52.PubMedCrossRefGoogle Scholar
  60. 60.
    Klemi PJ, Joensuu H, Eerola E. DNA aneuploidy in anaplastic carcinoma of the thyroid gland. Am J Clin Pathol. 1988;89(2):154–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Pinto AE, Silva G, Banito A, Leite V, Soares J. Aneuploidy and high S-phase as biomarkers of poor clinical outcome in poorly differentiated and anaplastic thyroid carcinoma. Oncol Rep. 2008;20(4):913–9.PubMedGoogle Scholar
  62. 62.
    Baldini E, Sorrenti S, Tartaglia F, Catania A, Palmieri A, Pironi D, et al. New perspectives in the diagnosis of thyroid follicular lesions. Int J Surg. 2017;41(Suppl 1):S7–S12.PubMedCrossRefGoogle Scholar
  63. 63.
    Cibas ES. Fine-needle aspiration in the work-up of thyroid nodules. Otolaryngol Clin N Am. 2010;43(2):257–71. vii–viii.CrossRefGoogle Scholar
  64. 64.
    Nishino M, Nikiforova M. Update on molecular testing for cytologically indeterminate thyroid nodules. Arch Pathol Lab Med. 2018;142(4):446–57.PubMedCrossRefGoogle Scholar
  65. 65.
    Vargas-Salas S, Martinez JR, Urra S, Dominguez JM, Mena N, Uslar T, et al. Genetic testing for indeterminate thyroid cytology: review and meta-analysis. Endocr Relat Cancer. 2018;25(3):R163–R77.PubMedCrossRefGoogle Scholar
  66. 66.
    Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013;98(11):E1852–60.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid. 2015;25(11):1217–23.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura M, Callenberg K, Santana-Santos L, et al. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer. 2018;124(8):1682–90.CrossRefGoogle Scholar
  69. 69.
    Jug RC, Datto MB, Jiang XS. Molecular testing for indeterminate thyroid nodules: performance of the Afirma gene expression classifier and ThyroSeq panel. Cancer Cytopathol. 2018;  https://doi.org/10.1002/cncy.21993.
  70. 70.
    Kloos RT. Molecular profiling of thyroid nodules: current role for the Afirma gene expression classifier on clinical decision making. Mol Imaging Radionucl Ther. 2017;26(Suppl 1):36–49.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Duh QY, Busaidy NL, Rahilly-Tierney C, Gharib H, Randolph G. A systematic review of the methods of diagnostic accuracy studies of the Afirma gene expression classifier. Thyroid. 2017;27(10):1215–22.PubMedCrossRefGoogle Scholar
  72. 72.
    Aragon Han P, Olson MT, Fazeli R, Prescott JD, Pai SI, Schneider EB, et al. The impact of molecular testing on the surgical management of patients with thyroid nodules. Ann Surg Oncol. 2014;21(6):1862–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Sacks WL, Bose S, Zumsteg ZS, Wong R, Shiao SL, Braunstein GD, et al. Impact of Afirma gene expression classifier on cytopathology diagnosis and rate of thyroidectomy. Cancer Cytopathol. 2016;124(10):722–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Guo HQ, Zhao H, Zhang ZH, Zhu YL, Xiao T, Pan QJ. Impact of molecular testing in the diagnosis of thyroid fine needle aspiration cytology: data from mainland China. Dis Markers. 2014;2014:912182.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Nicholson KJ, Yip L. An update on the status of molecular testing for the indeterminate thyroid nodule and risk stratification of differentiated thyroid cancer. Curr Opin Oncol. 2018;30(1):8–15.PubMedCrossRefGoogle Scholar
  76. 76.
    Bisarro Dos Reis M, Barros-Filho MC, Marchi FA, Beltrami CM, Kuasne H, Pinto CAL, et al. Prognostic classifier based on genome-wide DNA methylation profiling in well-differentiated thyroid tumors. J Clin Endocrinol Metab. 2017;102(11):4089–99.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Divisions of Anatomic Pathology and Molecular & Genomic Pathology, Departments of Pathology and Internal MedicineMichigan Medicine, University of MichiganAnn ArborUSA

Personalised recommendations