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NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer
Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3–9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of D...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896177/ https://www.ncbi.nlm.nih.gov/pubmed/31703244 http://dx.doi.org/10.3390/genes10110899 |
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author | Orois, Aida Gara, Sudheer K. Mora, Mireia Halperin, Irene Martínez, Sandra Alfayate, Rocio Kebebew, Electron Oriola, Josep |
author_facet | Orois, Aida Gara, Sudheer K. Mora, Mireia Halperin, Irene Martínez, Sandra Alfayate, Rocio Kebebew, Electron Oriola, Josep |
author_sort | Orois, Aida |
collection | PubMed |
description | Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3–9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred, with five cases of nonsyndromic FNMTC. Single Nucleotide Variants, and insertions and deletions that segregated with all the affected members, were analyzed by Sanger sequencing in 44 additional families with FNMTC (37 with two affected members, and seven with three or more affected members), as well as in an independent control group of 100 subjects. We identified the germline variant p. Asp31His in NOP53 gene (rs78530808, MAF 1.8%) present in all affected members in three families with nonsyndromic FNMTC, and not present in unaffected spouses. Our functional studies of NOP53 in thyroid cancer cell lines showed an oncogenic function. Immunohistochemistry exhibited increased NOP53 protein expression in tumor samples from affected family members, compared with normal adjacent thyroid tissue. Given the relatively high frequency of the variant in the general population, these findings suggest that instead of a causative gene, NOP53 is likely a low-penetrant gene implicated in FNMTC, possibly a modifier. |
format | Online Article Text |
id | pubmed-6896177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68961772019-12-23 NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer Orois, Aida Gara, Sudheer K. Mora, Mireia Halperin, Irene Martínez, Sandra Alfayate, Rocio Kebebew, Electron Oriola, Josep Genes (Basel) Article Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3–9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred, with five cases of nonsyndromic FNMTC. Single Nucleotide Variants, and insertions and deletions that segregated with all the affected members, were analyzed by Sanger sequencing in 44 additional families with FNMTC (37 with two affected members, and seven with three or more affected members), as well as in an independent control group of 100 subjects. We identified the germline variant p. Asp31His in NOP53 gene (rs78530808, MAF 1.8%) present in all affected members in three families with nonsyndromic FNMTC, and not present in unaffected spouses. Our functional studies of NOP53 in thyroid cancer cell lines showed an oncogenic function. Immunohistochemistry exhibited increased NOP53 protein expression in tumor samples from affected family members, compared with normal adjacent thyroid tissue. Given the relatively high frequency of the variant in the general population, these findings suggest that instead of a causative gene, NOP53 is likely a low-penetrant gene implicated in FNMTC, possibly a modifier. MDPI 2019-11-07 /pmc/articles/PMC6896177/ /pubmed/31703244 http://dx.doi.org/10.3390/genes10110899 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Orois, Aida Gara, Sudheer K. Mora, Mireia Halperin, Irene Martínez, Sandra Alfayate, Rocio Kebebew, Electron Oriola, Josep NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title | NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title_full | NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title_fullStr | NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title_full_unstemmed | NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title_short | NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer |
title_sort | nop53 as a candidate modifier locus for familial non-medullary thyroid cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896177/ https://www.ncbi.nlm.nih.gov/pubmed/31703244 http://dx.doi.org/10.3390/genes10110899 |
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