Genetic Mutations and Variants in the Susceptibility of Familial Non-Medullary Thyroid Cancer

Abstract

Thyroid cancer is the most frequent endocrine malignancy with the majority of cases derived from thyroid follicular cells and caused by sporadic mutations. However, when at least two or more first degree relatives present thyroid cancer, it is classified as familial non-medullary thyroid cancer (FNMTC) that may comprise 3–9% of all thyroid cancer. In this context, 5% of FNMTC are related to hereditary syndromes such as Cowden and Werner Syndromes, displaying specific genetic predisposition factors. On the other hand, the other 95% of cases are classified as non-syndromic FNMTC. Over the last 20 years, several candidate genes emerged in different studies of families worldwide. Nevertheless, the identification of a prevalent polymorphism or germinative mutation has not progressed in FNMTC. In this work, an overview of genetic alteration related to syndromic and non-syndromic FNMTC is presented.

Squamous Differentiation in the Thyroid: Metaplasia, Neoplasia, or Bystander?

“…This variant more frequently demonstrates RET -translocations, particularly in young patients. 30,31 Cribriform morular carcinoma, with its typical squamous morules, frequently demonstrates AFP mutations 32 and is now classified as a distinct entity from PTC (rather than a PTC variant) given its distinct morphologic, immunophenotypic, and molecular features. 33 Non-PTC associated entities with squamous differentiation include primary thyroid mucoepidermoid carcinoma, which in at least one case demonstrated the classic CRTC1 / MAML2 translocation associated with its salivary gland counterpart, 34,35 and sclerosing mucoepidermoid carcinoma with eosinophilia which has a notable lack of recurrent genomic alterations, including no BRAF , MAML2 , or common driver mutations identified to date.…”

Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street

“…The adenomatous polyposis coli protein has seven ß-catenin binding sites. Each such binding site has a sequence of 20-amino acid The proteins encoded by the genes involved in hereditary syndromes with thyroid cancer intervene in the maintenance of genome integrity, the DNA repair process, miRNA formation and maturation, various signalling pathways, and mitochondrial processes [13].…”

Il carcinoma familiare non midollare della tiroide non sindromico

“…Recentemente, studi di associazione genome-wide (GWAS) compiuti su un ampio numero di pazienti e di casicontrollo appartenenti a diversi tipi di popolazioni hanno condotto all'identificazione di ulteriori loci di suscettibilità per il FNMTC. Tra questi, i più riproducibili sono risultati: rs966423 (DIRC3), rs2439302 (NRG1), rs965513 (PTC-SC2/FOXE1), rs944289 (PTCSC3/NKX2-1) e rs116909374 (MBIP1) [13].…”