Title: Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro
Authors: BEU VOLPATO ClaudiaMARTÍNEZ-ALFARO MinervaCORVI RaffaellaGABUS CoralieSAUVIAGO SylvieFERRARI PietroBONORA ElenaDE GRANDI AlessandriROMEO Giovanni
Citation: CANCER RESEARCH vol. 68 no. 21 p. 8986-8992
Publisher: AMER ASSOC CANCER RESEARCH
Publication Year: 2008
JRC N°: JRC47809
ISSN: 0008-5472
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC47809
Type: Articles in periodicals and books
Abstract: Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remains unknown. The high prevalence of RET/PTC rearrangements in patients who have received external radiation and the in vitro induction of RET rearrangements in human cells suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. In order to assess whether RET is indeed more sensitive to radiations than other genomic regions we combined the COMET assay with fluorescence in situ hybridization (FISH), which allows the measurement of DNA damage of defined genomic regions in single cells. We have compared the initial DNA damage of the genomic regions of p53, PLA2A2, JAK2, MYC, CXCL12/SDF1, ABL and RET induced by ionizing radiation in a lymphoblastoid and in a foetal thyroid cell line. RET fragmentation was significantly higher than other genes fragmentation in both cell lines. Moreover, a differential distribution of signals within the COMET was observed with a higher percentage of RET fragments in the tail. Interestingly, RET was more susceptible to fragmentation in thyroid derived cells than in lymphoblasts. This enhanced initial fragility of RET to ionizing radiation may explain the high frequency of RET rearrangements found in radiation-induced tumors.
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