046 - Molecular pathogenesis of different histotypes of thyroid carcinoma: the role of NBS1 gene in the pathogenesis of solid tumors induced by ionizing radiation
Autor(s): S. Matera, S. Ursi, B. De Laurentiis, A. Marchetti, S. Martinotti, E. Toniato
Issue: RIMeL - IJLaM, Vol. 5, N. 3-S1, 2009 (MAF Servizi srl ed.)
Page(s): 46-51
Summary
The carcinoma of the thyroid is not a frequent disease and the diagnosis and cure are not simple. The studies of epidemiology do not seem to demonstrate (with the exception of the three rare variants of medullary carcinoma thyroid present in syndrome MEN II whose responsible gene is proto-oncogene the RET) the influence of inheritance factors. There are some risk factors that predispose to this tumor. The main factor of risk of the tumors of the thyroid is the exposure to the ionic radiation. Our research group has taken care of the role of gene NBS1 (gene that takes part to a system of repair of the DNA) in the pathogeneses of the inducing solid tumors induced by ionizing radiation. 20 cellular lines have been examined: 13 of breast cancer, 6 of ovarian cancer and one of colon cancer (cancers sensitive to the ionizing radiations). SW626 colon’s cellular line shows an insertion of 50 nucleotides from number 2 introne with formation of a codon of stop (TAG). The next step has been to localize the presence in vivo of lesions and/or alterations of nibrina’s RNA processing (in particular the location of the cryptic introne already described in SW626 colon’s cellular line). We analyzed the mRNA extracted from 16 biopsies of ovarian tumours, 10 biopsies of pulmonary tumours and 10 biopsies of normal pulmonary tissue. The cryptic introne has been found in 43.75% of the ovarian tumours and in all the pulmonary ones. Moreover, we have demonstrated that: 1) the expression of the introne is greater in the pulmonary tumoural tissue than in the normal pulmonary tissue one of the same patients; 2) the expression of the introne is greater in the normal tissue of the patients with pulmonary tumour compared with the blood of the volunteers. The evaluation of the mechanism and of the degree of DNA repair could be used as marker for directing therapy and assessing the disease progression. Key-words: double strand breakpoint, ionic radiation, nibrin.