Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784654566640320512 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8859953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Bioscientifica Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT demelloluiseduardobarbalho identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT carneirothaisenayaneribeiro identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT araujoalineneves identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT alvescamilaxavier identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT galantepedroalexandrefavoretto identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT buzattovanessacandiotti identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT dasgracasdealmeidamaria identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT vermeulenserpakarinamarques identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT delimavalesanchahelena identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT josedepintopaivafernando identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT brandaonetojose identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing AT ceruttijanetemaria identificationofnid1asanovelcandidatesusceptibilitygeneforfamilialnonmedullarythyroidcarcinomausingwholeexomesequencing |