Figure 4

Distinct characteristics between BRCA1 and BRCA2 germline mutated tumors. (A) Difference in subtype distribution. For the PAM50 subtype proportion and subtype colour of 20 tumors with BRCA1 germline mutation and 29 tumors with BRCA2 germline mutation, red represents basal-like, blue represents luminal (A + B), and green represents normal-like. (B) Difference in genomic instability pattern depending on BRCA germline mutation. In each group with BRCA1 and BRCA2 germline mutation, the extent of HRD score, the non-silent mutation rate, and IFN-γ signature were compared. In all cases, significantly higher levels were observed in the case of BRCA1 germline mutation. For calculating the p-value, the Wilcoxon rank-sum test was used, and the central line in the box plot represents the median. (C) Heat map showing gene expression in BRCA1 germline mutants and BRCA2 germline mutants. Based on the FPKM value for the genes, the intergroup fold change (FC = mean FPKM of BRCA2 germline mutants/mean FPKM of BRCA1 germline mutants) was calculated, and the genes with abs(log2(FC)) > 1.5 and Wilcoxon rank-sum test/Benjamini & Hochberg adjusted p-value < 0.05 were selected. The plotting was based on the column (gene) z-scale of log2FC values. (D) Activation of different functional pathways in cancer depending on BRCA1/2 germline mutation. Functional annotation analysis was conducted for the 79 genes that exhibited gene expression between the two groups of BRCA1 germline mutation and BRCA2 germline mutation, and p-value plot was used to visualize the ten commonly obtained functional pathways from the two tools. (E) Difference in DDR gene expression patterns for BRCA1 germline mutation and BRCA2 germline mutation groups. Among the 88 genes, those that exhibited an intergroup difference were grouped according to the pathway, and a significant expression difference in genes in the HR, BER, and FA pathways was observed. Expression values are colour-coded for each gene, the lowest expression value being bright green, the middle being black, and the highest being bright red. Tumor flags: Patients with BRCA1 hotspot or truncating germline mutation are labelled maroon, and patients with BRCA2 hotspot or truncating germline mutation are labelled black; Fold change: BRCA2-mutated group expression mean is divided by the BRCA1-mutated group, and then a log2 transformation is applied and then colour-coded. Deep red indicates a high positive log2 fold change, and deep blue indicates a high negative log2 fold change; p-value: Differences in expression among groups were compared using the rank-sum test. Genes that had a nominal p-value < 0.05 were labelled red, and the others white. Adjusted p-value: For all nominal p-values, multiple testing correction was performed by adjusting the p-values using the default p.adjust function in R.