LOBAL ENDOCRINOLOGY: Geographical variation in the profile of RET variants in patients with medullary thyroid cancer: a comprehensive revie

Autor(es)

Maciel, Rui M. B. ^[1] ; Maia, Ana Luiza ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Lab Mol & Translat Endocrinol, Escola Paulista Med, Sao Paulo, SP - Brazil

^[2] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Fac Med, Thyroid Unit, Porto Alegre, RS - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 186, n. 1, p. R15-R30, JAN 1 2022.
• Citações Web of Science: 0

Resumo

Genetic variability in humans is influenced by many factors, such as natural selection, mutations, genetic drift, and migrations. Molecular epidemiology evaluates the contribution of genetic risk factors in the etiology, diagnosis, and prevention of a particular disease. Few areas of medicine have been so clearly affected by genetic diagnosis and management as multiple neoplasia type 2 (MEN2), in which activating pathogenic variants in the RET gene results in the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism in nearly 98, 50, and 25% of gene carriers, respectively. Here, we aimed to collect RET genotyping data worldwide to analyze the distribution and frequency of RET variants from a global perspective. We show that the mutational spectrum of RET is observed worldwide. The codon 634 variants seem to be the most prevalent, but there are differences in the type of amino acid exchanges among countries and in the frequencies of the other RET codon variants. Most interestingly, studies using haplotype analysis or pedigree linkage have demonstrated that some pathogenic RET variants have been transmitted to offspring for centuries, explaining some local prevalence due to a founder effect. Unfortunately, after almost three decades after the causative role of the germline RET variants has been reported in hereditary MTC, comprehensive genotyping data remain limited to a few countries. The heterogeneity of RET variants justifies the need for a global effort to describe epidemiological data of families with MEN2 to further understand the genetic background and environmental circumstances that affect disease presentation. (AU)

• Processo FAPESP: 10/51547-1 - Carcinoma medular de tiroide hereditario: percepcao e atitude de pacientes, familiares e profissionais de saude sobre questoes bioeticas.
• Beneficiário: Rui Monteiro de Barros Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/01476-9 - Rastreamento de variantes de significado desconhecido (VUS) no proto-oncogene RET em pacientes com neoplasia endócrina múltipla tipo 2 e indivíduos saudáveis da população brasileira
• Beneficiário: Sergio Pereira de Almeida Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/06570-6 - Sequenciamento completo do exoma, Paired-end RNA e genoma: novos insights sobre a natureza genética do câncer de tiróide na idade adulta e na faixa etária pediátrica e aplicações na prática clínica
• Beneficiário: Janete Maria Cerutti
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/60402-1 - Carcinoma medular da tiróide: revisitação à clínica, à biologia molecular, à bioquímica e à biologia do desenvolvimento depois dos achados da genética molecular
• Beneficiário: Rui Monteiro de Barros Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Temático