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

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

Nature communications (2020-09-27)
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, Xiaoling Xu
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.

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