Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys

María Sánchez-Ares,Gemma Rodríguez-Carnero,Soledad Cameselle-García,José Antonio Puñal-Rodríguez,Ihab Abdulkader-Nallib,Carolina Beiras-Sarasquete,José Manuel Cameselle-Teijeiro

doi:10.3389/fendo.2022.829103

Abstract

Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.

Highlights

Thyroid cancer (TC) is the most increasing malignancy in the world, mainly due to the diagnosis of papillary thyroid carcinoma (PTC), which is the most common histological type of TC [1]
FNMTC is generally classified into two large groups: syndromic familial non-medullary thyroid cancer (S-FNMTC) when the TC is associated with syndromes that have extrathyroid manifestations, and non-syndromic familial non-medullary TC (NS-FNMTC) [3, 4]
Recent research shows that the genetic basis of NS-FNMTC is complex and heterogeneous, involving a monogenic, and a polygenic mode of inheritance in some families

Summary

Introduction

Thyroid cancer (TC) is the most increasing malignancy in the world, mainly due to the diagnosis of papillary thyroid carcinoma (PTC), which is the most common histological type of TC [1]. The age of the patients at the diagnosis of PTC (including papillary and follicular variants) ranged from 33 to 57 years (mean diagnosis age 44.6 yrs.) and small thyroid nodules were detected in another member of the affected families; in addition to PTC (43 yrs.), an invasive ductal breast cancer (36 yrs.) had been diagnosed in one of the patients with the c.619+1G>C mutation.

Results

Conclusion