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

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 generation...

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Autores principales: de Mello, Luis Eduardo Barbalho, Carneiro, Thaise Nayane Ribeiro, Araujo, Aline Neves, Alves, Camila Xavier, Galante, Pedro Alexandre Favoretto, Buzatto, Vanessa Candiotti, das Graças de Almeida, Maria, Vermeulen-Serpa, Karina Marques, de Lima Vale, Sancha Helena, José de Pinto Paiva, Fernando, Brandão-Neto, José, Cerutti, Janete Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859953/
https://www.ncbi.nlm.nih.gov/pubmed/34941562
http://dx.doi.org/10.1530/EC-21-0406
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author de Mello, Luis Eduardo Barbalho
Carneiro, Thaise Nayane Ribeiro
Araujo, Aline Neves
Alves, Camila Xavier
Galante, Pedro Alexandre Favoretto
Buzatto, Vanessa Candiotti
das Graças de Almeida, Maria
Vermeulen-Serpa, Karina Marques
de Lima Vale, Sancha Helena
José de Pinto Paiva, Fernando
Brandão-Neto, José
Cerutti, Janete Maria
author_facet de Mello, Luis Eduardo Barbalho
Carneiro, Thaise Nayane Ribeiro
Araujo, Aline Neves
Alves, Camila Xavier
Galante, Pedro Alexandre Favoretto
Buzatto, Vanessa Candiotti
das Graças de Almeida, Maria
Vermeulen-Serpa, Karina Marques
de Lima Vale, Sancha Helena
José de Pinto Paiva, Fernando
Brandão-Neto, José
Cerutti, Janete Maria
author_sort de Mello, Luis Eduardo Barbalho
collection PubMed
description 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.
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spelling pubmed-88599532022-02-23 Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing de Mello, Luis Eduardo Barbalho Carneiro, Thaise Nayane Ribeiro Araujo, Aline Neves Alves, Camila Xavier Galante, Pedro Alexandre Favoretto Buzatto, Vanessa Candiotti das Graças de Almeida, Maria Vermeulen-Serpa, Karina Marques de Lima Vale, Sancha Helena José de Pinto Paiva, Fernando Brandão-Neto, José Cerutti, Janete Maria Endocr Connect Research 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. Bioscientifica Ltd 2021-12-22 /pmc/articles/PMC8859953/ /pubmed/34941562 http://dx.doi.org/10.1530/EC-21-0406 Text en © The authors https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Research
de Mello, Luis Eduardo Barbalho
Carneiro, Thaise Nayane Ribeiro
Araujo, Aline Neves
Alves, Camila Xavier
Galante, Pedro Alexandre Favoretto
Buzatto, Vanessa Candiotti
das Graças de Almeida, Maria
Vermeulen-Serpa, Karina Marques
de Lima Vale, Sancha Helena
José de Pinto Paiva, Fernando
Brandão-Neto, José
Cerutti, Janete Maria
Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title_full Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title_fullStr Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title_full_unstemmed Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title_short Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
title_sort identification of nid1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859953/
https://www.ncbi.nlm.nih.gov/pubmed/34941562
http://dx.doi.org/10.1530/EC-21-0406
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