Fig. 1: Molecular profiling of BCLM by whole exome sequencing. | Nature Communications

Fig. 1: Molecular profiling of BCLM by whole exome sequencing.

From: Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype

Fig. 1

a Schematic showing the sites of material collected, created with BioRender.com. b Flowchart of sample processing pipeline. cfDNA, cell-free DNA; ctDNA, circulating tumour DNA, DTC, disseminated tumour cell; PDO, patient-derived organoid. c–e Samples underwent WES to identify mutation (exonic variants excluding synonymous SNVs, plus splice variants) and copy number aberration (CNA) events. c Chemotherapy-related COSMIC Single Base Substitution (SBS) mutational signatures compared between sites. Signature contributions of the six chemotherapy-related SBS signatures (SBS11, SBS17b, SBS28, SBS31, SBS35, SBS86) were compared between CSF cfDNA, plasma cfDNA, primary and metastasis tumour samples. Stacked bar plots display the mean signature contribution for each SBS signature across all samples in each category. Significantly different total chemotherapy-related SBS signature contribution between CSF and plasma cfDNA is shown (Mann-Whitney two-tailed test). All other comparisons were ns. d WES of paired CSF cfDNA samples collected at BCLM diagnosis and primary tumour samples (n = 17 pairs). Bars show proportion of total variants unique to CSF (median 47.8%; IQR 43.0–56.4%), unique to primary tumour (median 20.4%; IQR 16.6–31.5%) and shared (median 23.0%; IQR 13.8–33.7%). e WES of paired CSF cfDNA and plasma cfDNA samples collected at BCLM diagnosis (n = 11 pairs). Bars show proportion of total variants unique to CSF (median 24.6%; IQR 16.0–38.6%), unique to plasma (median 16.8%; IQR 11.3–26.6%) and shared (median 43.4%; IQR 24.2–65.1%).

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