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Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor
Single-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intratumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519681/ https://www.ncbi.nlm.nih.gov/pubmed/32978388 http://dx.doi.org/10.1038/s41467-020-18637-9 |
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author | Liu, Jianlin Adhav, Ragini Miao, Kai Su, Sek Man Mo, Lihua Chan, Un In Zhang, Xin Xu, Jun Li, Jianjie Shu, Xiaodong Zeng, Jianming Zhang, Xu Lyu, Xueying Pardeshi, Lakhansing Tan, Kaeling Sun, Heng Wong, Koon Ho Deng, Chuxia Xu, Xiaoling |
author_facet | Liu, Jianlin Adhav, Ragini Miao, Kai Su, Sek Man Mo, Lihua Chan, Un In Zhang, Xin Xu, Jun Li, Jianjie Shu, Xiaodong Zeng, Jianming Zhang, Xu Lyu, Xueying Pardeshi, Lakhansing Tan, Kaeling Sun, Heng Wong, Koon Ho Deng, Chuxia Xu, Xiaoling |
author_sort | Liu, Jianlin |
collection | PubMed |
description | Single-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intratumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing SNVs and CNVs simultaneously in bulk and single cells of premalignant tissues and tumors from mouse and human BRCA1-associated breast cancers, we discover an evolution process through which the tumors initiate from cells with SNVs affecting driver genes in the premalignant stage and malignantly progress later via CNVs acquired in chromosome regions with cancer driver genes. These events occur randomly and hit many putative cancer drivers besides p53 to generate unique genetic and pathological features for each tumor. Upon this, we finally identify a tumor metastasis suppressor Plekha5, whose deficiency promotes cancer metastasis to the liver and/or lung. |
format | Online Article Text |
id | pubmed-7519681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75196812020-10-14 Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor Liu, Jianlin Adhav, Ragini Miao, Kai Su, Sek Man Mo, Lihua Chan, Un In Zhang, Xin Xu, Jun Li, Jianjie Shu, Xiaodong Zeng, Jianming Zhang, Xu Lyu, Xueying Pardeshi, Lakhansing Tan, Kaeling Sun, Heng Wong, Koon Ho Deng, Chuxia Xu, Xiaoling Nat Commun Article Single-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intratumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing SNVs and CNVs simultaneously in bulk and single cells of premalignant tissues and tumors from mouse and human BRCA1-associated breast cancers, we discover an evolution process through which the tumors initiate from cells with SNVs affecting driver genes in the premalignant stage and malignantly progress later via CNVs acquired in chromosome regions with cancer driver genes. These events occur randomly and hit many putative cancer drivers besides p53 to generate unique genetic and pathological features for each tumor. Upon this, we finally identify a tumor metastasis suppressor Plekha5, whose deficiency promotes cancer metastasis to the liver and/or lung. Nature Publishing Group UK 2020-09-25 /pmc/articles/PMC7519681/ /pubmed/32978388 http://dx.doi.org/10.1038/s41467-020-18637-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Liu, Jianlin Adhav, Ragini Miao, Kai Su, Sek Man Mo, Lihua Chan, Un In Zhang, Xin Xu, Jun Li, Jianjie Shu, Xiaodong Zeng, Jianming Zhang, Xu Lyu, Xueying Pardeshi, Lakhansing Tan, Kaeling Sun, Heng Wong, Koon Ho Deng, Chuxia Xu, Xiaoling Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title | Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title_full | Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title_fullStr | Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title_full_unstemmed | Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title_short | Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor |
title_sort | characterization of brca1-deficient premalignant tissues and cancers identifies plekha5 as a tumor metastasis suppressor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519681/ https://www.ncbi.nlm.nih.gov/pubmed/32978388 http://dx.doi.org/10.1038/s41467-020-18637-9 |
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