Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing.

Autor:	de Mello LEB; Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., Carneiro TNR; Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Araujo AN; Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil., Alves CX; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., Galante PAF; Centro de Oncologia Molecular, Hospital Sírio-libanês, São Paulo, São Paulo, Brazil., Buzatto VC; Centro de Oncologia Molecular, Hospital Sírio-libanês, São Paulo, São Paulo, Brazil., das Graças de Almeida M; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.; Department of Clinical and Toxicological Analyses, Natal, Rio Grande do Norte, Brazil., Vermeulen-Serpa KM; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., de Lima Vale SH; Department of Clinical and Toxicological Analyses, Natal, Rio Grande do Norte, Brazil.; Department of Nutrition, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., José de Pinto Paiva F; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., Brandão-Neto J; Postgraduate Program in Health Sciences, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil., Cerutti JM; Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Endocrine connections [Endocr Connect] 2022 Jan 31; Vol. 11 (1). Date of Electronic Publication: 2022 Jan 31.
DOI:	10.1530/EC-21-0406
Abstrakt:	The genetics underlying non-syndromic familial non-medullary thyroid carcinoma (FNMTC) is still poorly understood. To identify susceptibility genes for FNMTC, we performed whole-exome sequencing (WES) in a Brazilian family affected by papillary thyroid carcinoma (PTC) in three consecutive generations. WES was performed in four affected and two unaffected family members. Manual inspection in over 100 previously reported susceptibility genes for FNMTC showed that no variants in known genes co-segregated with disease phenotype in this family. Novel candidate genes were investigated using PhenoDB and filtered using Genome Aggregation (gnomAD) and Online Archive of Brazilian Mutations (ABraOM) population databases. The missense variant p.Ile657Met in the NID1 gene was the only variant that co-segregated with the disease, while absent in unaffected family members and controls. The allele frequency for this variant was <0.0001 in the gnomAD and ABbraOM databases. In silico analysis predicted the variant to be deleterious or likely damaging to the protein function. Somatic mutations in NID1 gene were found in nearly 500 cases of different cancer subtypes in the intOGen platform. Immunohistochemistry analysis showed NID1 expression in PTC cells, while it was absent in normal thyroid tissue. Our findings were corroborated using data from the TCGA cohort. Moreover, higher expression of NID1 was associated with higher likelihood of relapse after treatment and N1b disease in PTCs from the TCGA cohort. Although replication studies are needed to better understand the role of this variant in the FNMTC susceptibility, the NID1 variant (c.1971T>G) identified in this study fulfills several criteria that suggest it as a new FNMTC predisposing gene.
Databáze:	MEDLINE
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