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

Author

Listed:
  • Jianlin Liu

    (University of Macau
    University of Macau)

  • Ragini Adhav

    (University of Macau
    University of Macau)

  • Kai Miao

    (University of Macau
    University of Macau)

  • Sek Man Su

    (University of Macau
    University of Macau)

  • Lihua Mo

    (University of Macau
    University of Macau)

  • Un In Chan

    (University of Macau
    University of Macau)

  • Xin Zhang

    (University of Macau
    University of Macau)

  • Jun Xu

    (University of Macau
    University of Macau)

  • Jianjie Li

    (University of Macau
    University of Macau)

  • Xiaodong Shu

    (University of Macau
    University of Macau)

  • Jianming Zeng

    (University of Macau
    University of Macau)

  • Xu Zhang

    (University of Macau
    University of Macau)

  • Xueying Lyu

    (University of Macau
    University of Macau)

  • Lakhansing Pardeshi

    (University of Macau
    University of Macau)

  • Kaeling Tan

    (University of Macau
    University of Macau)

  • Heng Sun

    (University of Macau
    University of Macau)

  • Koon Ho Wong

    (University of Macau
    University of Macau)

  • Chuxia Deng

    (University of Macau
    University of Macau)

  • Xiaoling Xu

    (University of Macau
    University of Macau)

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.

Suggested Citation

  • 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, 2020. "Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18637-9
    DOI: 10.1038/s41467-020-18637-9
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    Cited by:

    1. Jianjie Li & Xiaodong Shu & Jun Xu & Sek Man Su & Un In Chan & Lihua Mo & Jianlin Liu & Xin Zhang & Ragini Adhav & Qiang Chen & Yuqing Wang & Tingting An & Xu Zhang & Xueying Lyu & Xiaoling Li & Josh , 2022. "S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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