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Gene rearrangement and Chernobyl related thyroid cancers
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  • Regular Article
  • Open access
  • Published: 17 December 1999

Gene rearrangement and Chernobyl related thyroid cancers

  • M Santoro1,
  • G A Thomas2,
  • G Vecchio1,
  • G H Williams2,
  • A Fusco1,
  • G Chiappetta1,
  • V Pozcharskaya3,
  • T I Bogdanova4,
  • E P Demidchik3,
  • E D Cherstvoy3,
  • L Voscoboinik4,
  • N D Tronko4,
  • A Carss2,
  • H Bunnell2,
  • M Tonnachera5,
  • J Parma5,
  • J E Dumont5,
  • G Keller6,
  • H Höfler6 &
  • …
  • E D Williams2 

British Journal of Cancer volume 82, pages 315–322 (2000)Cite this article

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Abstract

The increase in thyroid carcinoma post-Chernobyl has been largely confined to a specific subtype of papillary carcinoma (solid/follicular). This subtype is observed predominantly in children under 10 in unirradiated populations, but maintains a high frequency in those aged 10–15 from those areas exposed to fallout from the Chernobyl accident. The aim of this study was to link morphology with molecular biology. We examined 106 papillary carcinomas from children under the age of 15 at operation. All were examined for rearrangements of the RET oncogene by reverse transcription polymerase chain reaction (RT-PCR); a subset of these cases were also examined for mutations of the three ras oncogenes, exon 10 of the thyroid stimulating hormone receptor, associated more usually with a follicular rather than papillary morphology, and exons 5, 6, 7 and 8 of the p53 gene, commonly involved in undifferentiated thyroid carcinoma. Rearrangements of the RET oncogene were found in 44% of papillary carcinomas in which we studied fresh material; none of the tumours examined showed mutation in any of the other genes. The two rearrangements resulting from inversion of part of chromosome 10 (PTC1 and PTC3) accounted for the majority of RET rearrangements identified, with PTC1 being associated with papillary carcinomas of the classic and diffuse sclerosing variants and PTC3 with the solid/follicular variant. © 2000 Cancer Research Campaign

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

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

    Article  CAS  PubMed  Google Scholar 

  • Beimfohr C, Klugbauer S, Demidchik EP, Lengfelder E and Rabes HM (1999) NTRK1 rearrangement in papillary thyroid carcinomas of children after the Chernobyl reactor accident. Int J Cancer 80: 842–847

    Article  CAS  PubMed  Google Scholar 

  • Bogdanova T, Bragarnik M, Tronko ND, Harach HR, Thomas GA and Williams ED (1996) The pathology of thyroid cancer in Ukraine post-Chernobyl. In: The Radiological Consequences of the Chernobyl Accident, Karaoglou A, Desmet G, Kelly GN, Menzel HG (eds), pp. 785–789. European Commission EUR 16544 EN

    Google Scholar 

  • Bounacer A, Wicker R, Caillou B, Cailleux AF, Sarasin A, Sclumberger M and Suarez HG (1997) High prevalence of activating ret proto-oncogene rearrangements from patients who had received external radiation. Oncogene 15: 1263–1273

    Article  CAS  PubMed  Google Scholar 

  • Challeton C, Bounacer A, Du Villard JA, Caillou B, De Vathaire F, Monier R, Schlumberger M and Suarez HG (1995) Pattern of ras and gsp oncogene mutations in radiation-associated human thyroid tumors. Oncogene 11: 601–603

    PubMed  CAS  Google Scholar 

  • Cherstvoy E, Pozcharskaya V, Harach HR, Thomas GA and Williams ED (1996) The pathology of childhood thyroid carcinoma in Belarus. In: The Radiological Consequences of the Chernobyl Accident, Karaoglou A, Desmet G, Kelly GN, Menzel HG (eds), pp. 779–784. European Commission EUR 16544 EN

    Google Scholar 

  • Fuggazzola L, Pilotti S, Pinchera A, Vorontsova TV, Mondellini P, Bongarzone I, Greco A, Astakhova L, Butti MG, Demidchik EP, Pacini F and Pierotti MA (1995) Oncogenic rearrangements of the ret proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. Cancer Res 55: 5617–5620

    Google Scholar 

  • Grieco A, Pierotti MA, Bongarzone I, Pagliardini J, Lanzi C and Della Porta G (1992) Trk-T1 is a novel oncogene formed by the fusion of TPR and Trk genes in human papillary cancer. Oncogene 7: 237–242

    Google Scholar 

  • Harach HR and Williams ED (1995) Childhood thyroid cancer in England and Wales. Br J Cancer 72: 777–783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hillebrandt S, Streffer C, Demidchik EP, Biko J and Reiners C (1997) Polymorphisms in the p53 gene in thyroid tumours and blood samples of children from areas in Belarus. Mutat Res 381: 201–207

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Seyama T, Mizuno T, Tsuyama N, Hayashi T, Hayashi Y, Dohi K, Nakamura N and Akiyama M (1992) Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res 52: 1369–1371

    PubMed  CAS  Google Scholar 

  • Ito T, Seyama T, Iwamoto KS, Hayashi T, Mizuno T, Tsuyama N, Dohi K, Nakamura N and Akiyama M (1993) In vitro irradiation is able to cause RET oncogene rearrangement. Cancer Res 53: 2940–2943

    PubMed  CAS  Google Scholar 

  • Ito T, Seyama T, Iwamoto KS, Mizuno T, Tronko ND, Komissarenko IV, Cherstvoy ED, Satow Y, Takiechi N, Dohi K and Akiyama M (1994) Activated ret oncogene in thyroid cancers of children from areas contaminated by Chernobyl accident. Lancet 344: 259

    PubMed  CAS  Google Scholar 

  • Jacob P, Goulko G, Heidenrich WF, Likhtarev I, Kairo I, Tronko ND, Bogdanora TI, Kenigsberg J, Buglova E, Drozdovitch V, Goloneva A, Demidchik EP, Balanov M, Zvonova I and Beral V (1998) Thyroid risk to children calculated. Nature 392: 31–32

    Article  CAS  PubMed  Google Scholar 

  • Jhiang SM, Sagartz JE, Tong Q, Parker TJ, Capen CC, Cho JY, Xing S and Ledent C (1996) Targetted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology 137: 375–378

    Article  CAS  PubMed  Google Scholar 

  • Kazakov VS, Demidchik EP and Astakhova LN (1992) Thyroid cancers after Chernobyl. Nature 359: 21

    Article  CAS  PubMed  Google Scholar 

  • Klugbauer S, Lengfelder E, Demidchik EP and Rabes HM (1995) High prevalence of ret rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident. Oncogene 11: 2459–2467 5620

    PubMed  CAS  Google Scholar 

  • Klugbauer S, Demidchik EP, Lengfelder E and Rabes HM (1998) Detection of a novel type of ret rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved ret-fused gene RFG5. Cancer Res 58: 198–203

    PubMed  CAS  Google Scholar 

  • Lemoine NR, Mayall ES, Wyllie FS, Williams ED, Goyns M, Stringer BMJ and Wynford-Thomas D (1989) High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 2: 159–164

    Google Scholar 

  • Likhtarev IA, Sobolev BG, Kairo IA Tronko ND, Bogdanova TI, Olenic VA, Epshtein EV and Beral V (1995) Thyroid cancer in Ukraine. Nature 375: 365

    Article  CAS  PubMed  Google Scholar 

  • Lohmann D, Putz B, Reich U, Bohm J, Prauer H and Hofler H (1993) Mutational spectrum of the p53 gene in human small-cell lung cancer and relationship to clinicopathological data. Am J Pathol 142: 907–915

    PubMed  PubMed Central  CAS  Google Scholar 

  • Manenti G, Pilotti S, Re FC, Della Porta G and Pierotti MA (1994) Selective activation of ras oncogenes in follicular and undifferentiated thyroid carcinomas. Eur J Cancer 30A: 987–993

    Article  CAS  PubMed  Google Scholar 

  • Nikiforov YE, Nikiforova MN, Gnepp DR and Fagin JA (1996) Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. Oncogene 13: 687–693

    PubMed  CAS  Google Scholar 

  • Nikiforov YE, Rowland JM, Bove KE, Monforte-Munoz H and 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

    PubMed  CAS  Google Scholar 

  • Ohno M, Endo T, Ohta K, Gunji K and Onaya T (1995) Point mutations in the thyrotropin receptor in human thyroid tumors. Thyroid 5: 97–100

    Article  CAS  PubMed  Google Scholar 

  • Parkin DM, Stiller CA, Bieber A, Draper GJ, Terracini B and Young YL (eds) (1988). International Incidence of Childhood Cancer, IARC Scientific Publications No 87. International Association for Research an Cancer: Lyon

    Book  Google Scholar 

  • Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont J and Vassart G (1995) Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3′,5′-monophosphate and inositol phosphate-Ca2+cascades. Mol Endocrinol 9: 725–733

    PubMed  CAS  Google Scholar 

  • Powell DJ, Russell J, Nibu K, Li G, Rhee E, Lioa M, Goldstein M, Keane WM, Santoro M, Fusco A and Rothstein J (1998) The ret/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res 58: 5523–5528

    PubMed  CAS  Google Scholar 

  • Russo D, Arturi F, Schlumberger M, Caillou B, Monier R, Filetti S and Suarez HG (1995) Activating mutations of the TSH receptor in differentiated thyroid carcinomas. Oncogene 11: 1907–1911

    PubMed  CAS  Google Scholar 

  • Sankaranarayanan K (1991) Ionizing radiation and genetic risks. III. Nature of spontaneous and radiation-induced mutations in mammalian in vitro systems and mechanisms of induction of mutations by radiation. Mutat Res 258: 75–97

    Article  CAS  PubMed  Google Scholar 

  • Santoro M, Carlomango F and Hay ID (1992) Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype. J Clin Invest 89: 1517–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santoro M, Chiappetta G, Cerrato A, Salvatore D, Zhang L, Manzo G, Picone A, Portella G, Santelli G, Vecchio G and Fusco A (1996) Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. Oncogene 12: 1821

    PubMed  CAS  Google Scholar 

  • Shi YF, Zou MJ, Schmidt H, Juhasz F, Stensky V, Robb D and Farid NR (1991) High rates of ras codon 61 mutation in thyroid tumors in an iodide-deficient area. Cancer Res 51: 2690–2693

    PubMed  CAS  Google Scholar 

  • Smida J, Zitzelsberger H, Kellerer AM, Lehmann L, Minkus G, Negele T, Spelsberg F, Hieber L, Demidchik EP, Lengfelder E and Bauchinger M (1997) p53 mutations in childhood thyroid tumours from Belarus and in thyroid tumours without radiation history. Int J Cancer 73: 802–807

    Article  CAS  PubMed  Google Scholar 

  • Smida J, Salassidisk K, Hieber L, Zitelsberger H, Kellere AM, Demidchik EP, Negele T, Spelsberg F, Lengfelder E, Weiner M and Bauchinger M (1999) Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus. Int J Cancer 80: 32–38

    Article  CAS  PubMed  Google Scholar 

  • Suarez HG, du Villard JA, Severino M, Caillou B, Schlumberger M, Tubiana M, Parmentier C and Monier R (1990) Presence of mutations in all three ras genes in human thyroid tumors. Oncogene 5: 565–570

    PubMed  CAS  Google Scholar 

  • Suchy B, Waldmann V, Klugbauer S and Rabes HM (1998) Absence of RAS and p53 mutations in thyroid carcinomas of children after Chernobyl in contrast to adult thyroid tumours. Br J Cancer 77: 952–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugg SL, Ezzat S, Rosen IB, Freeman JL and Asa SL (1998) Distinct multiple ret/ptc gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab 83: 4116–4122

    PubMed  CAS  Google Scholar 

  • Thomas GA, Bunnell H, Cook HA, Williams ED, Nerovnya A, Cherstvoy ED, Tronko ND, Bogdanova TI, Chiappetta G, Viglietto G, Pentimalli F, Salvatore G, Fusco A, Santoro M and Vecchio G (1999) High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid/follicular variant. J Clin Endocrinol Metab,

  • Waldmann V and Rabes HM (1997) Absence of Gsα gene mutations in childhood thyroid tumors after Chernobyl in contrast to sporadic adult thyroid neoplasia. Cancer Res 57: 2358–2361

    PubMed  CAS  Google Scholar 

  • Wright PA, Williams ED, Lemoine NR and Wynford-Thomas D (1991) Radiation-associated and ‘spontaneous’ human thyroid carcinomas show a different pattern of ras oncogene mutation. Oncogene 6: 471–473

    PubMed  CAS  Google Scholar 

  • Viglietto G, Chiappetta G, Martinez-Tello FJ, Fukunaga FH, Tallini G, Rigopoulou D, Visconti R, Mastro A, Santoro M and Fusco A (1995) RET/PTC oncogene activation is an early event in thyroid carcinogenesis. Oncogene 11: 1207–1210

    PubMed  CAS  Google Scholar 

  • Williams ED (1996) Effects on the thyroid in populations exposed to radiation as a result of the Chernobyl accident. In: One Decade After Chernobyl. IAEA: 207–230

    Google Scholar 

  • Williams GH, Rooney S, Thomas GA, Cummins G and Williams ED (1996) RET activation in adult and childhood papillary thyroid carcinoma using a reverse transcriptase-n-polymerase chain reaction approach on archival-nested material. Br J Cancer 74: 585–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woessner S, Sole F, Perez-Losada A, Florensa L and Vila RM (1996) Trisomy 12 is a rare cytogenetic finding in typical chronic lymphocytic leukemia. Leuk Res 20: 369–374

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Centro di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare, e Moleculare, Universita di Napoli, Italy

    M Santoro, G Vecchio, A Fusco & G Chiappetta

  2. Thyroid Carcinogenesis Group, University of Cambridge, Strangeways Research Laboratory, Wort's Causeway, Cambridge, CB1 4RN, UK

    G A Thomas, G H Williams, A Carss, H Bunnell & E D Williams

  3. Minsk State Medical Institute, Minsk, Belarus

    V Pozcharskaya, E P Demidchik & E D Cherstvoy

  4. Institute of Endocrinology and Metabolism, Kiev, Ukraine

    T I Bogdanova, L Voscoboinik & N D Tronko

  5. IRIHBN, Free University of Brussels, Belgium

    M Tonnachera, J Parma & J E Dumont

  6. Institute for Pathology, Technical University of Munich, Germany

    G Keller & H Höfler

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  11. L Voscoboinik
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Santoro, M., Thomas, G., Vecchio, G. et al. Gene rearrangement and Chernobyl related thyroid cancers. Br J Cancer 82, 315–322 (2000). https://doi.org/10.1054/bjoc.1999.0921

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  • Received: 24 March 1999

  • Revised: 22 July 1999

  • Accepted: 25 August 1999

  • Published: 17 December 1999

  • Issue date: 01 January 2000

  • DOI: https://doi.org/10.1054/bjoc.1999.0921

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Keywords

  • thyroid cancer
  • Chernobyl
  • gene rearrangement
  • ref
  • oncogenes

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