Fig. 5: Driver events of CNVs and tumor evolution of Brca1-deficient breast tumor revealed by scWES.

a DNA copy-number profiles based on the developmental stages of single cells from mice (n = 98 cells). VWMG-virgin wild-type mammary gland cells from 4-month-old mouse; 476WMG-476 wild-type mammary gland cell from 11-month-old tumor-bearing mouse #476. b Top: oncoplot summarizing SNVs in potential driver genes (Scube3, Akt1s1, Psmb3, Cdc5l, Npm1, etc.) (Fig. 4b; Supplementary Fig. 4b) and potential driver CNVs (amplification of chromosome 11) (a) of mouse 476. Bottom: tumor evolution model of mouse 476 based on potential driver SNV and CNV results. c Top: oncoplot summarizing SNVs in potential driver genes (Arhegf11, Plekha5, Bub1, etc.) (Fig. 4b; Supplementary Fig. 4c) and potential driver CNVs (amplification of chromosome 1, 6, 16, and deletion of chromosome 4, 14) (a) of mouse 153. Bottom: tumor evolution model of mouse 153 based on potential driver SNV and CNV results. d DNA copy number profiles of single cells from the BRCA1-MT PDX models (n = 37 cells). TM00089, which carries a frameshift variant: BRCA1-V757fs; and TM00091, which carries a common pathogenic missense variant C61G in BRCA1 RING domain. e–h ddPCR analysis of amplification of chromosome 11 (Ppm1d) in 476MG and 476PT (e), amplification of chromosome 1 (Cxcr4) in 153MG and 153PT (f), amplification of chromosome 1 (ARHGEF11) and chromosome 17 (PPM1D) in TM00091 (g), amplification of Arhgef11 in 4T1 cell line (h). Rpp30/RPP30 was used as a reference gene for normalization. Three technical replicates were performed. i Measurement of tumor volume after implantation of 4T1 Control and 4T1-Arhgef11-KO cells into mammary fat pat (4 × 10⁶ tumor cells per injection, n = 8 mice per group). Data are reported as the mean ± SD with two-way ANOVA analysis with Dunnett’s test, ****P < 0.0001. j Image of tumors in (i) at the endpoint of measurement. Error bars represent SD.