Aim: Utilize breast cancer samples in the same patient to indicate breast cancer development. Patients & methods: We performed whole-exome analysis of spatially independent ductal carcinoma in situ (DCIS) and invasive ductal carcinoma samples from the same breast. Results: In VEGF pathway, we observed two genes disrupted in DCIS, while another four (including ACTN2) mutated in invasive ductal carcinoma. When looked up TCGA database, we identified seven breast cancer patients with ACTN2 somatic mutations and observed a dramatic decrease in the overall survival time in ACTN2 mutant patients (p = 0.0182). A further finding in the TCGA database shows that breast cancer patients with ≥2 mutated genes in VEGF pathways showed worse prognosis (p = 0.0013). Conclusion: TCGA database and special case could inform each other to reveal DCIS developmental rules.
Keywords: ACTN mutation; VEGF pathway; ductal carcinoma; invasive ductal carcinoma; precision medicine.