The ret/PTC1 Rearrangement is a Common Feature of Chernobyl-Associated Papillary Thyroid Carcinomas from Belarus

Abstract

An increase in the incidence of papillary thyroid cancer has been documented in individuals exposed to Chernobyl fallout in 1986. Experiments using cultured human cells have suggested that radiation can induce the ret/PTC1 rearrangement involving the ret proto-oncogene. To test the hypothesis that the ret/PTC1 rearrangement is involved in the pathogenesis of Chernobyl-associated papillary thyroid carcinomas, we studied a panel of 31 cases from Belarus. All individuals lived in fallout-contaminated oblasts (regions) of Belarus at the time of the accident: Gomel (n = 13), Brest (n = 12), Minsk (n = 4), and Grodno (n = 2). All were under age 20 at the time of the accident; 20 were born between 1982 and 1986. Individual thyroid radiation doses were estimated at 1.1 to 110 rem. Patients underwent surgery in Minsk in 1996. Fifteen patients had locally advanced disease (stage T4). The majority had regional lymph node involvement (stage N1, n = 27). There were no distant metastases. Surgical specimens were frozen at -80 degrees C, RNA was extracted and cDNA prepared. The polymerase chain reaction (PCR) was performed with specific primers for ret/PTC1, and c-ret and GAPDH as controls. Controls were positive in all 31 cases. Nine cases yielded a positive PCR product for the ret/PTC1 rearrangement (29%). Thus, the ret/PTC1 rearrangement is a feature of some Chernobyl-associated papillary thyroid cancers, and is one possible mechanism involved in the pathogenesis of these cancers.

ret/PTC Activation Is Not Associated with Individual Radiation Dose Estimates in a Pilot Study of Neoplastic Thyroid Nodules Arising in Russian Children and Adults Exposed to Chernobyl Fallout

“…The rate of ret=PTC activation in the children in this study is clearly lower than the 84-87% activation rates detected in PTC cases arising following external beam irradiation (15,24,25), and may be lower than the 30-86% activation rates detected in PTCs developing after exposure to Chernobyl fallout during childhood that have been reported to date (3)(4)(5)(6)(7)(8)(9)(10)(11). However,…”

“…Analyses of radiation-associated PTC specimens usually find a higher rate of ret=PTC activation ranging from 30% to 86% (2). Even though ionizing radiation has been shown to induce ret=PTC rearrangements in thyroid cancer cell culture models, other variables such as ethnic background, age at diagnosis, and latency period between radiation exposure and development of clinically evident PTC may also have a significant impact on the prevalence rate of ret=PTC activation reported in clinical samples (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients

“…Most studies have focused on PTCs that developed rapidly in children from contaminated areas of Belarus and Ukraine (Fugazzola et al 1995, Klugbauer et al 1995, Nikiforov et al 1997, Pisarchik et al 1998a, 1998b, Smida et al 1999, Thomas et al 1999, Rabes et al 2000, Santoro et al 2000, Elisei et al 2001. Only three studies included PTC from adults living in contaminated areas, but none attempted to compare with adults living in supposedly non-affected areas of the same regions (Klugbauer et al 1995, Smida et al 1999, Rabes et al 2000.…”

“…According to one report, PTCs in children under 10 in 1986 showed an unusually high prevalence of ret /PTC3 (Klugbauer et al 1995). Like people receiving external radiation for therapeutic purposes, PTCs in older children and adults exposed to Chernobyl fallout exhibited an increase in ret /PTC1 (Fugazzola et al 1995, Klugbauer et al 1995, Bounacer et al 1997, Pisarchik et al 1998b.…”

Aspectos moleculares do câncer tiroideano

“…A ativação do protoncogene RET/PTC1 e RET/PTC4, por exemplo, tem sido observada com freqüências elevadas em populações que foram expostas à radioatividade (8,9,42,43,92).…”