Investigation of Loss of Heterozygosity and SNP Frequencies in the RET Gene in Papillary Thyroid Carcinoma

Abstract

In both medullary carcinoma and papillary carcinoma of the thyroid, altered expression of the RET gene is implicated in tumorigenesis. Recent studies suggest that loss of heterozygosity (LOH) at the G691S SNP may be associated with tumors from patients with a history of radiation exposure. We investigated LOH for three RET SNPs (G691S, S904S, and L769L) in tumor and normal tissue from 46 patients from Ukraine and Belarus who were exposed to radioactive fallout following the Chernobyl nuclear accident and were operated for papillary thyroid carcinoma between 1995 and 2000. Normal tissue from 28 patients was heterozygous for at least one SNP; DNA from the corresponding tumor samples was also heterozygous, indicating that no LOH had taken place. To assess SNP frequencies in a radiation-associated thyroid cancer cohort, we investigated a further 68 unpaired post-Chernobyl samples. For G691S, there was considerable deviation from Hardy-Weinberg equilibrium; more detailed analysis showed that this was linked to age at onset of disease. Among younger patients, the distribution of genotypes conformed to Hardy-Weinberg equilibrium; among older patients, we observed marked deviation (p = 0.0072), with significant over-representation of the rare S allele relative to the younger groups (Fisher's exact, p = 0.0233). This suggests that SNPs in the RET oncogene may play a role in sporadic papillary thyroid carcinoma.

Functional RET G691S polymorphism in cutaneous malignant melanoma

“…RET p was originally found in radiation-induced thyroid tumors and sporadic medullary thyroid cancers (Bounacer et al, 2002; Elisei et al, 2004). In this report, we identified high frequency of RET p in cutaneous melanomas, particularly and more frequently in DMs (non-DMs: 31%, DMs: 61%), whereas RET p has been detected in only 15–20% of the normal population (Bounacer et al, 2002; Ceccherini et al, 1994; Elisei et al, 2004; Stephens et al, 2005). As not all DMs are neurotropic, we did not find RET p in all DMs.…”

Single Nucleotide Polymorphism rs17849071 G/T in the PIK3CA Gene Is Inversely Associated with Follicular Thyroid Cancer and PIK3CA Amplification

“…For example, the L769L polymorphism of the RET gene seemed to affect the onset age of familial MTC [24]. Certain RET gene SNPs were shown to be associated with an increased risk of differentiated thyroid cancer [25], [26]. A XRCC3 18067T polymorphic allele was similarly shown to be associated with differentiated thyroid cancer [27].…”

BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients

“…Another explanation for the non-HWE frequencies could be loss of heterozygosity (LOH), a common occurence in tumourigenesis. LOH can, in fact, be implicated in SNP frequency deviations from HWE (Stephens et al 2005), although LOH has not been conWrmed for the BIRC5 locus (17q25) yet.…”