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Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer
Background: Distant metastasis is a rare occurrence in thyroid cancer, and it can be associated with poor prognosis. The genomic repertoires of various solid malignancies have previously been reported but remain underexplored in metastatic papillary thyroid cancer (PTC). Furthermore, whether distant...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983753/ https://www.ncbi.nlm.nih.gov/pubmed/31668133 http://dx.doi.org/10.1089/thy.2019.0052 |
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author | Masoodi, Tariq Siraj, Abdul K. Siraj, Sarah Azam, Saud Qadri, Zeeshan Albalawy, Wafaa N. Parvathareddy, Sandeep Kumar Al-Sobhi, Saif S. Al-Dayel, Fouad Alkuraya, Fowzan S. Al-Kuraya, Khawla S. |
author_facet | Masoodi, Tariq Siraj, Abdul K. Siraj, Sarah Azam, Saud Qadri, Zeeshan Albalawy, Wafaa N. Parvathareddy, Sandeep Kumar Al-Sobhi, Saif S. Al-Dayel, Fouad Alkuraya, Fowzan S. Al-Kuraya, Khawla S. |
author_sort | Masoodi, Tariq |
collection | PubMed |
description | Background: Distant metastasis is a rare occurrence in thyroid cancer, and it can be associated with poor prognosis. The genomic repertoires of various solid malignancies have previously been reported but remain underexplored in metastatic papillary thyroid cancer (PTC). Furthermore, whether distant metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. Methods: We performed whole-exome sequencing on 14 matched distant metastases, primary PTC tumors, and normal tissues. Point mutations, copy number alterations, cancer cell fractions, and mutational signatures were defined using the state-of-the-art bioinformatics methods. All likely deleterious variants were validated by orthogonal methods. Results: Genomic differences were observed between primary and distant metastatic deposits, with a median of 62% (range 21–92%) of somatic mutations detected in metastatic tissues, but absent from the corresponding primary tumor sample. Mutations in known driver genes including BRAF, NRAS, and HRAS were shared and preferentially clonal in both sites. However, likely deleterious variants affecting DNA methylation and transcriptional repression signaling genes including SIN3A, RBBP1, and CHD4 were found to be restricted in the metastatic lesions. Moreover, a mutational signature shift was observed between the mutations that are specific or enriched in the metastatic and primary lesions. Conclusions: Primary PTC and distant metastases differ in their range of somatic alterations. Genomic analysis of distant metastases provides an opportunity to identify potentially clinically informative alterations not detected in primary tumors, which might influence decisions for personalized therapy in PTC patients with distant metastasis. |
format | Online Article Text |
id | pubmed-6983753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-69837532020-02-11 Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer Masoodi, Tariq Siraj, Abdul K. Siraj, Sarah Azam, Saud Qadri, Zeeshan Albalawy, Wafaa N. Parvathareddy, Sandeep Kumar Al-Sobhi, Saif S. Al-Dayel, Fouad Alkuraya, Fowzan S. Al-Kuraya, Khawla S. Thyroid Thyroid Cancer and Nodules Background: Distant metastasis is a rare occurrence in thyroid cancer, and it can be associated with poor prognosis. The genomic repertoires of various solid malignancies have previously been reported but remain underexplored in metastatic papillary thyroid cancer (PTC). Furthermore, whether distant metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. Methods: We performed whole-exome sequencing on 14 matched distant metastases, primary PTC tumors, and normal tissues. Point mutations, copy number alterations, cancer cell fractions, and mutational signatures were defined using the state-of-the-art bioinformatics methods. All likely deleterious variants were validated by orthogonal methods. Results: Genomic differences were observed between primary and distant metastatic deposits, with a median of 62% (range 21–92%) of somatic mutations detected in metastatic tissues, but absent from the corresponding primary tumor sample. Mutations in known driver genes including BRAF, NRAS, and HRAS were shared and preferentially clonal in both sites. However, likely deleterious variants affecting DNA methylation and transcriptional repression signaling genes including SIN3A, RBBP1, and CHD4 were found to be restricted in the metastatic lesions. Moreover, a mutational signature shift was observed between the mutations that are specific or enriched in the metastatic and primary lesions. Conclusions: Primary PTC and distant metastases differ in their range of somatic alterations. Genomic analysis of distant metastases provides an opportunity to identify potentially clinically informative alterations not detected in primary tumors, which might influence decisions for personalized therapy in PTC patients with distant metastasis. Mary Ann Liebert, Inc., publishers 2020-01-01 2020-01-21 /pmc/articles/PMC6983753/ /pubmed/31668133 http://dx.doi.org/10.1089/thy.2019.0052 Text en © Tariq Masoodi et al., 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited. |
spellingShingle | Thyroid Cancer and Nodules Masoodi, Tariq Siraj, Abdul K. Siraj, Sarah Azam, Saud Qadri, Zeeshan Albalawy, Wafaa N. Parvathareddy, Sandeep Kumar Al-Sobhi, Saif S. Al-Dayel, Fouad Alkuraya, Fowzan S. Al-Kuraya, Khawla S. Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title | Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title_full | Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title_fullStr | Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title_full_unstemmed | Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title_short | Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer |
title_sort | whole-exome sequencing of matched primary and metastatic papillary thyroid cancer |
topic | Thyroid Cancer and Nodules |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983753/ https://www.ncbi.nlm.nih.gov/pubmed/31668133 http://dx.doi.org/10.1089/thy.2019.0052 |
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