Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor

Jianlin Liu, Ragini Adhav, Kai Miao, Sek Man Su, Lihua Mo, Un In Chan, Xin Zhang, Jun Xu, Jianjie Li, Xiaodong Shu, Jianming Zeng, Xu Zhang, Xueying Lyu, Lakhansing Pardeshi, Kaeling Tan, Heng Sun, Koon Ho Wong, Chuxia Deng () and Xiaoling Xu ()
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Jianlin Liu: University of Macau
Ragini Adhav: University of Macau
Kai Miao: University of Macau
Sek Man Su: University of Macau
Lihua Mo: University of Macau
Un In Chan: University of Macau
Xin Zhang: University of Macau
Jun Xu: University of Macau
Jianjie Li: University of Macau
Xiaodong Shu: University of Macau
Jianming Zeng: University of Macau
Xu Zhang: University of Macau
Xueying Lyu: University of Macau
Lakhansing Pardeshi: University of Macau
Kaeling Tan: University of Macau
Heng Sun: University of Macau
Koon Ho Wong: University of Macau
Chuxia Deng: University of Macau
Xiaoling Xu: University of Macau

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18637-9

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