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Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor
Liu,Jianlin1,2; Adhav,Ragini1,2; Miao,Kai1,2; Su,Sek Man1,2; Mo,Lihua1,2; Chan,Un In1,2; Zhang,Xin1,2; Xu,Jun1,2; Li,Jianjie1,2; Shu,Xiaodong1,2; Zeng,Jianming1,2; Zhang,Xu1,2; Lyu,Xueying1,2; Pardeshi,Lakhansing1,3; Tan,Kaeling1,3; Sun,Heng1,2; Wong,Koon Ho1,3; Deng,Chuxia1,2; Xu,Xiaoling1,2
2020-12-01
Source PublicationNature Communications
ISSN2041-1723
Volume11Issue:1
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.

DOI10.1038/s41467-020-18637-9
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000573737400007
Scopus ID2-s2.0-85091658171
Fulltext Access
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDeng,Chuxia; Xu,Xiaoling
Affiliation1.Cancer Centre,Faculty of Health Sciences,University of Macau,Macau,China
2.Centre for Precision Medicine Research and Training,Faculty of Health Sciences,University of Macau,Macau,China
3.Genomics,Bioinformatics & Single Cell Analysis Core,Faculty of Health Sciences,University of Macau,Macau,China
First Author AffilicationCancer Centre;  Faculty of Health Sciences
Corresponding Author AffilicationCancer Centre;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Liu,Jianlin,Adhav,Ragini,Miao,Kai,et al. Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor[J]. Nature Communications,2020,11(1).
APA 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.(2020).Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor.Nature Communications,11(1).
MLA Liu,Jianlin,et al."Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor".Nature Communications 11.1(2020).
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