Background: Single nucleotide polymorphisms (SNPs) may function as modifiers of the RET proto-oncogene, resulting in the expression of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). We present 2 non-related Italian-American families (Family 1, n = 107; Family 2, n = 31) with the RET V804M mutation. We have correlated the presence of specific SNPs and the rare RET V804M mutation to MTC, C-cell hyperplasia (CCH), and PTC.
Methods: Sequencing was performed on exons 10, 11, and 13-16 of the RET proto-oncogene. The presence of MTC, CCH, and PTC were correlated to specific SNPs.
Results: In both families, 3 SNPs in exon 11 (G691S), exon 13 (L769L), and exon 15 (S904S) were detected in 100% of patients with overt MTC. The SNP L769L was present in all patients including patients with PTC, MTC, and CCH.
Conclusion: SNP analysis revealed a similar pattern between the 2 families. SNPs in exon 11 (G691S) and exon 15 (S904S) appear to influence the development of MTC. A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation.
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Article Synopsis
- This review focuses on the relationship between pathogenic variants related to medullary thyroid cancer (MTC) and multiple endocrine neoplasia type 2 (MEN2), especially considering their connection to cutaneous lichen amyloidosis (CLA).
- It highlights that most MEN2A patients with CLA have a specific pathogenic variant at codon 634, yet the connection between CLA and MTC remains poorly understood despite being recognized for over thirty years.
- The findings indicate that CLA usually appears early in life, often before MTC is diagnosed, and the relationship between mutations and CLA presentation can vary even within the same family.
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