Array comparative genomic hybridisation analysis of gamma-irradiated human thyrocytes.
The susceptibility of thyroid epithelium to radiation-induced carcinogenesis is well recognised. In this context, thyroid carcinogenesis is associated with specific somatic ret/papillary thyroid carcinoma (PTC) rearrangements and morphologically with the papillary phenotype. Previous studies have demonstrated the possibility of inducing ret rearrangements in vitro using X-rays. The purpose of our study was to assess whether gamma (gamma) radiation using a Caesium 137 source can induce specific ret rearrangements in a human thyroid epithelial cell culture model. We further hypothesised that if radiation-induced thyroid carcinogenesis is associated with non-random rearrangement events, then DNA copy gain and loss induced by irradiation may also occur in a non-random manner. We irradiated SV40-immortalised human thyroid epithelial cells with incremental doses of gamma-radiation and, using TaqMan reverse-transcription polymerase chain reaction, looked for the presence of the common ret rearrangements. Cohorts showing evidence of ret/PTC chimeric transcripts were further analysed using microarray comparative genomic hybridisation (CGH) to detect copy gain and loss associated with radiation. Four Grays of gamma-radiation was sufficient to induce ret/PTC-3. In this model, transcripts of ret/PTC-1 were not detected, and we suggest that the type of radiation may influence the resulting rearrangement that occurs. Using array CGH, we have demonstrated a predominant pattern of subtelomeric deletions occurring in association with this radiation cohort and raise the possibility that chromosome 10 may be a hotspot for radiation-induced damage for as yet unknown reasons.
Finn
Stephen P
SP
Department of Histopathology Research, University of Dublin, Trinity College, Room 35/72, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital , James's Street, Dublin 8, Ireland. sfinn@gofree.indigo.ie
Smyth
Paul
P
O'regan
Esther
E
Cahill
Susanne
S
Flavin
Richard
R
O'leary
John
J
Sheils
Orla
O
D002291:Carcinoma, Papillary / Q000235:genetics*; D002460:Cell Line; D005720:Gamma Rays; D015321:Gene Rearrangement; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D013961:Thyroid Gland / Q000473:pathology / Q000528:radiation effects*; D013964:Thyroid Neoplasms / Q000235:genetics*
D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human