Skip to main content

Molecular Changes in Radiation Induced Thyroid Carcinomas in Mice

  • Conference paper
  • First Online:
  • 704 Accesses

Abstract

Thyroid carcinomas arising from follicular epithelial cells are the most common endocrine malignancy in man. During studies performed on the population of the Marshall-Islands and after the accident at the Chernobyl nuclear power plant in 1986 a large increase in benign thyroid nodules and thyroid cancer, especially among children was shown. Thyroid follicular carcinomas are categorised into 3 histotypes: papillary, follicular, and undifferentiated (anaplastic). Papillary thyroid carcinomas are the predominant type of the thyroid cancer in patients exposed to external radiation, particularly in children. The classic oncogenic genetic alterations commonly seen in thyroid cancer include RET/PTC rearrangements, Ras point-mutations, PAX8-peroxisome proliferator-activated receptor γ (PPARg) fusion oncogene and BRAF mutation. For some families that share the FNMTC syndrome (familiar follicular nonmedullary thyroid carcinoma) a predisposition to thyroid tumors has been described. The genes responsible for FNMTC have been identified through linkage analyses of the affected families, TCO (thyroid tumors with cell oxyphilia), PRN1, and NHTC1. This study investigates gene changes in radiation induced follicular thyroid carcinoma. Following low dose exposure of the thyroid by off-targeted irradiation of the alpha-emitter 227Thorium, 5 cases of Follicular thyroid carcinomas (FTC) and 1 case of thyroid hyperplasia developed in a highly susceptible mouse strain. In such cases, Comparative Genomic Hybridization (CGH) for numerical changes was performed on the whole genome. Copy number loss affecting the entire chromosome 14 in 3 out of 6 cases was observed. A similar pattern of chromosome 14 deletions was already reported in thyroid tumours of other mouse strains following high-dose exposure or oncogene activation and therefore suggests that this deletion is not associated with genetic predisposition in different mouse strains to thyroid tumourigenesis.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Baverstock K, Egloff B, Pinchera A, Ruchti C, Williams D (1992) Thyroid cancer after Chernobyl. Nature 359:21–22

    Article  CAS  Google Scholar 

  2. Fagin JA (1997) Familial nonmedullary thyroid carcinoma–the case for genetic susceptibility. J Clin Endocrinol Metab 82:342–344

    Article  CAS  Google Scholar 

  3. Fagin JA (2002) Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol Endocrinol 16:903–911

    Article  CAS  Google Scholar 

  4. Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP (1993) High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179–184

    Article  CAS  Google Scholar 

  5. Farid NR (2004) Molecular basis of thyroid cancer, pp 87–90

    Google Scholar 

  6. Hölzwimmer GC (2007) Histologische und molekulargenetische Untersuchungen von strahleninduzierten Schilddrüsentumoren im Mausmodelled^eds. Ludwig-Maximilians-Universität, München

    Google Scholar 

  7. Komminoth P (1997) The RET proto-oncogene in medullary and papillary thyroid carcinoma. Molecular features, pathophysiology and clinical implications. Virchows Arch 431:1–9

    Article  CAS  Google Scholar 

  8. Lin X, Finkelstein SD, Zhu B, Silverman JF (2008) Molecular analysis of multifocal papillary thyroid carcinoma. J Mol Endocrinol 41:195–203

    Article  CAS  Google Scholar 

  9. McKay JD, Thompson D, Lesueur F, Stankov K, Pastore A, Watfah C, Strolz S, Riccabona G, Moncayo R, Romeo G, Goldgar DE (2004) Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer. J Med Genet 41:407–412

    Article  CAS  Google Scholar 

  10. Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, Ohtsuru A, Saenko VA, Kanematsu T, Yamashita S (2003) Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab 88:4393–4397

    Article  CAS  Google Scholar 

  11. Nikiforov Y, Gnepp DR, Fagin JA (1996) Thyroid lesions in children and adolescents after the Chernobyl disaster: implications for the study of radiation tumorigenesis. J Clin Endocrinol Metab 81:9–14

    Article  CAS  Google Scholar 

  12. Nikiforov YE, Rowland JM, Bove KE, Monforte-Munoz H, Fagin JA (1997) Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res 57:1690–1694

    CAS  Google Scholar 

  13. Pal T, Vogl FD, Chappuis PO, Tsang R, Brierley J, Renard H, Sanders K, Kantemiroff T, Bagha S, Goldgar DE, Narod SA, Foulkes WD (2001) Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study. J Clin Endocrinol Metab 86:5307–5312

    Article  CAS  Google Scholar 

  14. Richter H, Braselmann H, Hieber L, Thomas G, Bogdanova T, Tronko N, Zitzelsberger H (2004) Chromosomal imbalances in post-chernobyl thyroid tumors. Thyroid 14:1061–1064

    Article  Google Scholar 

  15. Ried T, Liyanage M, du Manoir S, Heselmeyer K, Auer G, Macville M, Schrock E (1997) Tumor cytogenetics revisited: comparative genomic hybridization and spectral karyotyping. J Mol Med 75:801–814

    Article  CAS  Google Scholar 

  16. Sadetzki S, Chetrit A, Lubina A, Stovall M, Novikov I (2006) Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea capitis. J Clin Endocrinol Metab 91:4798–4804

    Article  CAS  Google Scholar 

  17. Santoro M, Melillo RM, Fusco A (2006) RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture. Eur J Endocrinol 155:645–653

    Article  CAS  Google Scholar 

  18. Shvarts S, Sevo G, Tasic M, Shani M, Sadetzki S (2010) The tinea capitis campaign in Serbia in the 1950s. Lancet Infect Dis 10(8):571–576

    Article  Google Scholar 

  19. Stsjazhko VA, Tsyb AF, Tronko ND, Souchkevitch G, Baverstock KF (1995) Childhood thyroid cancer since accident at Chernobyl. BMJ 310:801

    CAS  Google Scholar 

  20. Sturgeon C, Clark OH (2005) Familial nonmedullary thyroid cancer. Thyroid 15:588–593

    Article  Google Scholar 

  21. Sumner D (2007) Health effects resulting from the Chernobyl accident. Med Confl Surviv 23:31–45

    Article  Google Scholar 

  22. Takahashi T, Trott KR, Fujimori K, Simon SL, Ohtomo H, Nakashima N, Takaya K, Kimura N, Satomi S, Schoemaker MJ (1997) An investigation into the prevalence of thyroid disease on Kwajalein Atoll Marshall Islands. Health Phys 73:199–213

    Article  CAS  Google Scholar 

  23. Takahashi T, Simon SL, Trott KR, Fujimori K, Nakashima N, Arisawa K, Schoemaker MJ (1999) A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study. Tohoku J Exp Med 187:363–375

    Article  CAS  Google Scholar 

  24. Takahashi T, Fujimori K, Simon SL, Bechtner G, Edwards R, Trott KR (1999) Thyroid nodules, thyroid function and dietary iodine in the Marshall islands. Int J Epidemiol 28:742–749

    Article  CAS  Google Scholar 

  25. Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245–262

    Article  CAS  Google Scholar 

Download references

Acknowledgments

I would like to thank Head of the Department of Radiation Cytogenetics Helmholtz Center Munich Prof. Dr. H. Zitzelsberger and to the Head of the Master course in Radiation Biology University College London Prof. Claus R. Trott.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. Klymenko .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this paper

Cite this paper

Klymenko, O., Heiliger, KJ., Vasconcellos, I.G., Dalke, C., Atkinson, M.J., Rosemann, M. (2012). Molecular Changes in Radiation Induced Thyroid Carcinomas in Mice. In: Mothersill, C., Korogodina, V., Seymour, C. (eds) Radiobiology and Environmental Security. NATO Science for Peace and Security Series C: Environmental Security. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1939-2_25

Download citation

Publish with us

Policies and ethics