Molecular profiling of lymphovascular invasive cancer cells in TNBC using G&T-seq

We comprehensively analyzed the genomic and transcriptional profiles of 97 laser capture microdissection (LCM) isolated cell clusters from a single patient with triple negative breast cancer (TNBC). By performing simultaneous genome and transcriptome amplification and sequencing (G&T-seq) on these clusters, we identified four RNA cancer cell clones that were directly linked to DNA clone counterparts. We also detected the presence of a lymphovascular invasive (LVI) clone characterized by chromosome instability (CIN), and a specific genomic and transcriptional pattern shared with several primary cancer cell clusters. Furthermore, combination phylogeny analysis pointed to three evolutionarily distinct metastatic pathways in this patient, and hub gene evaluation found the down regulation of ribosomal protein mRNA to be a potential prognostic marker for breast cancer.