Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast

Qianqian Shi, Kang Shao, Hongqin Jia, Boyang Cao, Weidong Li, Shichen Dong, Jian Liu, Kailiang Wu, Meng Liu, Fangfang Liu, Hanlin Zhou, Jianke Lv, Feng Gu, Luyuan Li, Shida Zhu, Shuai Li (), Guibo Li () and Li Fu ()
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Qianqian Shi: Tianjin Medical University Cancer Institute and Hospital
Kang Shao: BGI-Shenzhen
Hongqin Jia: Tianjin Medical University Cancer Institute and Hospital
Boyang Cao: BGI-Shenzhen
Weidong Li: Tianjin Medical University Cancer Institute and Hospital
Shichen Dong: BGI-Shenzhen
Jian Liu: Tianjin Medical University Cancer Institute and Hospital
Kailiang Wu: Tianjin Medical University Cancer Institute and Hospital
Meng Liu: BGI-Shenzhen
Fangfang Liu: Tianjin Medical University Cancer Institute and Hospital
Hanlin Zhou: BGI-Shenzhen
Jianke Lv: Tianjin Medical University Cancer Institute and Hospital
Feng Gu: Tianjin Medical University Cancer Institute and Hospital
Luyuan Li: Nankai University
Shida Zhu: BGI-Shenzhen
Shuai Li: Tianjin Medical University Cancer Institute and Hospital
Guibo Li: BGI-Shenzhen
Li Fu: Tianjin Medical University Cancer Institute and Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Invasive micropapillary carcinoma (IMPC) has very high rates of lymphovascular invasion and lymph node metastasis and has been reported in several organs. However, the genomic mechanisms underlying its metastasis are unclear. Here, we perform whole-genome sequencing of tumor cell clusters from primary IMPC and paired axillary lymph node metastases. Cell clusters in multiple lymph node foci arise from a single subclone of the primary tumor. We find evidence that the monoclonal metastatic ancestor in primary IMPC shares high frequency copy-number loss of PRDM16 and IGSF9 and the copy number gain of ALDH2. Immunohistochemistry analysis further shows that low expression of IGSF9 and PRDM16 and high expression of ALDH2 are associated with lymph node metastasis and poor survival of patients with IMPC. We expect these genomic and evolutionary profiles to contribute to the accurate diagnosis of IMPC.

Date: 2022
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DOI: 10.1038/s41467-021-27794-4

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