Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer
Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PT...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213497/ https://www.ncbi.nlm.nih.gov/pubmed/30241415 http://dx.doi.org/10.3390/ijms19102867 |
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author | Lee, Woo Kyung Lee, Seul Gi Yim, Seung Hyuk Kim, Daham Kim, Hyunji Jeong, Seonhyang Jung, Sang Geun Jo, Young Suk Lee, Jandee |
author_facet | Lee, Woo Kyung Lee, Seul Gi Yim, Seung Hyuk Kim, Daham Kim, Hyunji Jeong, Seonhyang Jung, Sang Geun Jo, Young Suk Lee, Jandee |
author_sort | Lee, Woo Kyung |
collection | PubMed |
description | Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease. |
format | Online Article Text |
id | pubmed-6213497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62134972018-11-14 Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer Lee, Woo Kyung Lee, Seul Gi Yim, Seung Hyuk Kim, Daham Kim, Hyunji Jeong, Seonhyang Jung, Sang Geun Jo, Young Suk Lee, Jandee Int J Mol Sci Article Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease. MDPI 2018-09-21 /pmc/articles/PMC6213497/ /pubmed/30241415 http://dx.doi.org/10.3390/ijms19102867 Text en © 2018 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 Lee, Woo Kyung Lee, Seul Gi Yim, Seung Hyuk Kim, Daham Kim, Hyunji Jeong, Seonhyang Jung, Sang Geun Jo, Young Suk Lee, Jandee Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title | Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title_full | Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title_fullStr | Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title_full_unstemmed | Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title_short | Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer |
title_sort | whole exome sequencing identifies a novel hedgehog-interacting protein g516r mutation in locally advanced papillary thyroid cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213497/ https://www.ncbi.nlm.nih.gov/pubmed/30241415 http://dx.doi.org/10.3390/ijms19102867 |
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