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...

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Autores principales: Lee, Woo Kyung, Lee, Seul Gi, Yim, Seung Hyuk, Kim, Daham, Kim, Hyunji, Jeong, Seonhyang, Jung, Sang Geun, Jo, Young Suk, Lee, Jandee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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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.
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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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