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A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here,...

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Autores principales: Srivastava, Aayushi, Miao, Beiping, Skopelitou, Diamanto, Kumar, Varun, Kumar, Abhishek, Paramasivam, Nagarajan, Bonora, Elena, Hemminki, Kari, Försti, Asta, Bandapalli, Obul Reddy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352431/
https://www.ncbi.nlm.nih.gov/pubmed/32492864
http://dx.doi.org/10.3390/cancers12061441
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author Srivastava, Aayushi
Miao, Beiping
Skopelitou, Diamanto
Kumar, Varun
Kumar, Abhishek
Paramasivam, Nagarajan
Bonora, Elena
Hemminki, Kari
Försti, Asta
Bandapalli, Obul Reddy
author_facet Srivastava, Aayushi
Miao, Beiping
Skopelitou, Diamanto
Kumar, Varun
Kumar, Abhishek
Paramasivam, Nagarajan
Bonora, Elena
Hemminki, Kari
Försti, Asta
Bandapalli, Obul Reddy
author_sort Srivastava, Aayushi
collection PubMed
description Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we report in silico analyses and in vitro experiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of the Protection of Telomeres 1 (POT1) gene in one of the families. The results showed a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293T cells carrying POT1 p.V29L showed increased telomere length in comparison to wild-type cells, suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. While one germline mutation in POT1 has already been reported in a melanoma-prone family with prevalence of thyroid cancers, we report the first of such mutations in a family affected solely by NMTCs, thus expanding current knowledge on shelterin complex-associated cancers.
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spelling pubmed-73524312020-07-15 A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer Srivastava, Aayushi Miao, Beiping Skopelitou, Diamanto Kumar, Varun Kumar, Abhishek Paramasivam, Nagarajan Bonora, Elena Hemminki, Kari Försti, Asta Bandapalli, Obul Reddy Cancers (Basel) Article Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we report in silico analyses and in vitro experiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of the Protection of Telomeres 1 (POT1) gene in one of the families. The results showed a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293T cells carrying POT1 p.V29L showed increased telomere length in comparison to wild-type cells, suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. While one germline mutation in POT1 has already been reported in a melanoma-prone family with prevalence of thyroid cancers, we report the first of such mutations in a family affected solely by NMTCs, thus expanding current knowledge on shelterin complex-associated cancers. MDPI 2020-06-01 /pmc/articles/PMC7352431/ /pubmed/32492864 http://dx.doi.org/10.3390/cancers12061441 Text en © 2020 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
Srivastava, Aayushi
Miao, Beiping
Skopelitou, Diamanto
Kumar, Varun
Kumar, Abhishek
Paramasivam, Nagarajan
Bonora, Elena
Hemminki, Kari
Försti, Asta
Bandapalli, Obul Reddy
A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title_full A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title_fullStr A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title_full_unstemmed A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title_short A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer
title_sort germline mutation in the pot1 gene is a candidate for familial non-medullary thyroid cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352431/
https://www.ncbi.nlm.nih.gov/pubmed/32492864
http://dx.doi.org/10.3390/cancers12061441
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