Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus

Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT‐PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of 69% for the Belarussian cases, but of only 19% in the German patients. In contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1) similar to that in earlier investigations (diagnosed 1991–94) was obtained for cases included in our study that were diagnosed in 1993/94. The present data suggest that ret/PTC3 may be typical for radiation‐associated childhood PTC with a short latency period, whereas ret/PTC1 may be a marker for later‐occurring PTC of radiation‐exposed adults and children. Int. J. Cancer 80:32–38, 1999. © 1999 Wiley‐Liss, Inc.

[1]  H. Zitzelsberger,et al.  p53 mutations in childhood thyroid tumors from Belarus and in theyroid tumors without radiation history , 1997, International journal of cancer.

[2]  A. Bounacer,et al.  High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation , 1997, Oncogene.

[3]  Y. Nikiforov,et al.  Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. , 1997, Cancer research.

[4]  G. Brabant,et al.  ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? , 1997, The Journal of clinical endocrinology and metabolism.

[5]  M. Pierotti,et al.  Molecular and biochemical analysis of RET/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer. , 1996, Oncogene.

[6]  H. Rabes,et al.  A new form of RET rearrangement in thyroid carcinomas of children after the Chernobyl reactor accident. , 1996, Oncogene.

[7]  S. Asa,et al.  ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? , 1996, The Journal of clinical endocrinology and metabolism.

[8]  M. Nikiforova,et al.  Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. , 1996, Oncogene.

[9]  A. Schneider,et al.  p53 gene mutations in radiation-induced thyroid cancer. , 1996, The Journal of clinical endocrinology and metabolism.

[10]  G. Williams,et al.  RET activation in adult and childhood papillary thyroid carcinoma using a reverse transcriptase-n-polymerase chain reaction approach on archival-nested material. , 1996, British Journal of Cancer.

[11]  J. Jardillier,et al.  Ret and trk proto-oncogene activation in thyroid papillary carcinomas in French patients from the Champagne-Ardenne region. , 1996, Clinical biochemistry.

[12]  C. Streffer,et al.  Mutations in the p53 tumour suppressor gene in thyroid tumours of children from areas contaminated by the Chernobyl accident. , 1996, International journal of radiation biology.

[13]  H. Rabes,et al.  High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident. , 1995, Oncogene.

[14]  A. Pinchera,et al.  Oncogenic rearrangements of the RET proto-oncogene in papillary thyroid carcinomas from children exposed to the Chernobyl nuclear accident. , 1995, Cancer research.

[15]  M. Santoro,et al.  Molecular defects in thyroid carcinomas: role of the RET oncogene in thyroid neoplastic transformation. , 1995, European journal of endocrinology.

[16]  J H Lubin,et al.  Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. , 1995, Radiation research.

[17]  Takashi lto,et al.  Activated RET oncogene in thyroid cancers of children from areas contaminated by Chernobyl accident , 1994, The Lancet.

[18]  D. Wilkinson,et al.  Tuberculosis treatment programmes in low-income countries , 1994, The Lancet.

[19]  M. Borrello,et al.  Frequent activation of ret protooncogene by fusion with a new activating gene in papillary thyroid carcinomas. , 1994, Cancer research.

[20]  M. Santoro,et al.  Molecular characterization of RET/PTC3; a novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma. , 1994, Oncogene.

[21]  T. Seyama,et al.  In vitro irradiation is able to cause RET oncogene rearrangement. , 1993, Cancer research.

[22]  B. Pasternack,et al.  Thyroid cancer among persons given X-ray treatment in infancy for an enlarged thymus gland. , 1993, American journal of epidemiology.

[23]  C. Carcano,et al.  Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A , 1993, Molecular and cellular biology.

[24]  S. Kingman.  Thyroid cancer rises after Chernobyl. , 1992, BMJ.

[25]  V. S. Kazakov,et al.  Thyroid cancer after Chernobyl , 1992, Nature.

[26]  Y. Yoshimoto,et al.  Thyroid cancer: epidemiological study of thyroid cancer in A-bomb survivors from extended life span study cohort in Hiroshima. , 1991, Journal of radiation research.

[27]  M. Santoro,et al.  PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas , 1990, Cell.

[28]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.