Genome profiles of pathologist-defined cell clusters by multiregional LCM and G&T-seq in one triple-negative breast cancer patient

Zhongyi Zhu; Weiwei Wang; Feng Lin; Tracy Jordan; Guibo Li; Sveta Silverman; Si Qiu; Anil Abraham Joy; Chao Chen; Deanna L Hockley; Xi Zhang; Qing Zhou; Lynne M Postovit; Xiuqing Zhang; Yong Hou; John R Mackey; Bo Li; Gane Ka-Shu Wong

doi:10.1016/j.xcrm.2021.100404

Genome profiles of pathologist-defined cell clusters by multiregional LCM and G&T-seq in one triple-negative breast cancer patient

Cell Rep Med. 2021 Oct 19;2(10):100404. doi: 10.1016/j.xcrm.2021.100404.

Authors

Zhongyi Zhu^{1

2}, Weiwei Wang^{3

4}, Feng Lin¹, Tracy Jordan³, Guibo Li¹, Sveta Silverman⁵, Si Qiu¹, Anil Abraham Joy⁶, Chao Chen¹, Deanna L Hockley⁶, Xi Zhang¹, Qing Zhou¹, Lynne M Postovit⁷, Xiuqing Zhang¹, Yong Hou¹, John R Mackey⁶, Bo Li¹, Gane Ka-Shu Wong^{1

3

8}

Affiliations

¹ BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
² College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada.
⁴ Geneis, Bldg A, 5 Guangshun North Street, Beijing 100102, China.
⁵ Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB T6G 2H7, Canada.
⁶ Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada.
⁷ Department of Oncology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
⁸ Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.

Abstract

Pathological examination is the gold standard for cancer diagnosis, and breast tumor cells are often found in clusters. We report a case study on one triple-negative breast cancer (TNBC) patient, analyzing tumor development, metastasis, and prognosis with simultaneous DNA and RNA sequencing of pathologist-defined cell clusters from multiregional frozen sections. The cell clusters are isolated by laser capture microdissection (LCM) from primary tumor tissue, lymphatic vessels, and axillary lymph nodes. Data are reported for a total of 97 cell clusters. A combination of tumor cell-cluster clonality and phylogeny reveals 3 evolutionarily distinct pathways for this patient, each associated with a unique mRNA signature, and each correlated with disparate survival outcomes. Hub gene analysis indicates that extensive downregulation of ribosomal protein mRNA is a potential marker of poor prognosis in breast cancer.

Keywords: G&T-seq; LCM; lymphovascular invasion; metastasis; triple-negative breast cancer.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Cell Aggregation / genetics
Cell Lineage / genetics*
Clone Cells
DNA, Neoplasm / genetics*
DNA, Neoplasm / metabolism
Disease Progression
Epithelial Cells / classification
Epithelial Cells / metabolism
Epithelial Cells / pathology
Fatal Outcome
Female
Gene Expression Regulation, Neoplastic
Genome, Human*
High-Throughput Nucleotide Sequencing
Humans
Lymph Nodes / metabolism
Lymph Nodes / pathology
Lymphatic Metastasis
Lymphatic Vessels / metabolism
Lymphatic Vessels / pathology
Lymphocytes / classification
Lymphocytes / metabolism
Lymphocytes / pathology
Phylogeny
Prognosis
RNA, Neoplasm / genetics*
RNA, Neoplasm / metabolism
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism
Triple Negative Breast Neoplasms / diagnosis*
Triple Negative Breast Neoplasms / genetics*
Triple Negative Breast Neoplasms / metabolism
Triple Negative Breast Neoplasms / pathology
Young Adult

Substances

DNA, Neoplasm
RNA, Neoplasm
Ribosomal Proteins