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

Summary 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.
Graphical abstract
Highlights Pathologically diverse cell clusters share genomic and transcriptomic profiles Transcriptome-defined clones are more complex than genome-defined clones Three distinct pathways were inferred, each with disparate survival outcomes Lower expression of ribosomal proteins may be an indicator of poor prognosis
Zhu et al. reveal the complexity of tumor development, metastasis, and prognosis by simultaneous DNA and RNA sequencing of pathologist-defined cell clusters, excised through laser capture microdissection from multiregional frozen sections of a triple-negative breast cancer patient.