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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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