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Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing

Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial N...

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Autores principales: Tous, Cristina, Muñoz-Redondo, Carmen, Bravo-Gil, Nereida, Gavilan, Angela, Fernández, Raquel María, Antiñolo, Juan, Navarro-González, Elena, Antiñolo, Guillermo, Borrego, Salud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178269/
https://www.ncbi.nlm.nih.gov/pubmed/37175550
http://dx.doi.org/10.3390/ijms24097843
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author Tous, Cristina
Muñoz-Redondo, Carmen
Bravo-Gil, Nereida
Gavilan, Angela
Fernández, Raquel María
Antiñolo, Juan
Navarro-González, Elena
Antiñolo, Guillermo
Borrego, Salud
author_facet Tous, Cristina
Muñoz-Redondo, Carmen
Bravo-Gil, Nereida
Gavilan, Angela
Fernández, Raquel María
Antiñolo, Juan
Navarro-González, Elena
Antiñolo, Guillermo
Borrego, Salud
author_sort Tous, Cristina
collection PubMed
description Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial NMTC shows a high degree of genetic heterogeneity. Herein, we aimed to identify susceptibility genes for familial NMTC and non-RET MTC by whole exome sequencing in 58 individuals belonging to 18 Spanish families with these carcinomas. After data analysis, 53 rare candidate segregating variants were identified in 12 of the families, 7 of them located in previously TC-associated genes. Although no common mutated genes were detected, biological processes regulating functions such as cell proliferation, differentiation, survival and adhesion were enriched. The reported functions of the identified genes together with pathogenicity and structural predictions, reinforced the candidacy of 36 of them, suggesting new loci related to TC and novel genotype–phenotype correlations. Therefore, our strategy provides clues to possible molecular mechanisms underlying familial forms of MTC and NMTC. These new molecular findings and clinical data of patients may be helpful for the early detection, development of tailored therapies and optimizing patient management.
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spelling pubmed-101782692023-05-13 Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing Tous, Cristina Muñoz-Redondo, Carmen Bravo-Gil, Nereida Gavilan, Angela Fernández, Raquel María Antiñolo, Juan Navarro-González, Elena Antiñolo, Guillermo Borrego, Salud Int J Mol Sci Article Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial NMTC shows a high degree of genetic heterogeneity. Herein, we aimed to identify susceptibility genes for familial NMTC and non-RET MTC by whole exome sequencing in 58 individuals belonging to 18 Spanish families with these carcinomas. After data analysis, 53 rare candidate segregating variants were identified in 12 of the families, 7 of them located in previously TC-associated genes. Although no common mutated genes were detected, biological processes regulating functions such as cell proliferation, differentiation, survival and adhesion were enriched. The reported functions of the identified genes together with pathogenicity and structural predictions, reinforced the candidacy of 36 of them, suggesting new loci related to TC and novel genotype–phenotype correlations. Therefore, our strategy provides clues to possible molecular mechanisms underlying familial forms of MTC and NMTC. These new molecular findings and clinical data of patients may be helpful for the early detection, development of tailored therapies and optimizing patient management. MDPI 2023-04-25 /pmc/articles/PMC10178269/ /pubmed/37175550 http://dx.doi.org/10.3390/ijms24097843 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tous, Cristina
Muñoz-Redondo, Carmen
Bravo-Gil, Nereida
Gavilan, Angela
Fernández, Raquel María
Antiñolo, Juan
Navarro-González, Elena
Antiñolo, Guillermo
Borrego, Salud
Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title_full Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title_fullStr Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title_full_unstemmed Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title_short Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing
title_sort identification of novel candidate genes for familial thyroid cancer by whole exome sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178269/
https://www.ncbi.nlm.nih.gov/pubmed/37175550
http://dx.doi.org/10.3390/ijms24097843
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