Background: Somatic reversion mutations in either BRCA1/2 has been reported to lead to the resistance of platinum-based chemotherapy or PARPi. In this study we try to analyze the secondary somatic mutations in BRCA1/2 in patients with germline mutations. Methods: Using gene-panel target-captore next generation sequencing, we analyzed the secondary somatic mutations from 86 patients with BRCA1/2 germline mutations. Results: Eighty-six cases with BRCA1/2 gremline mutations were identified. Secondary somatic mutations restoring BRCA1/2 were identified in 7 patients, including 2 breast cancer, 3 ovarian cancer, 1 prostate cancer and 1cholangiocarcinoma patient. For these seven patients, five had been treated with platinum-based chemotherapy without PARPi and the other two (patient 1 and 2) with PARPi (olaparib). Patient 1 and 2 both received targeting therapy of PARP inhibitor olaparib after the germline BRCA1/2 mutation was detected. About six months later, plasma ctDNA was sequenced. Result showed that the germline mutations remained and additional larger deletions was detected. These secondary somatic mutations are not predicted to significantly affect the BRCA1/2 protein, and are likely to cause resistance to platinum-based chemotherapy or PARPi therapy by restoring BRCA1/2 ORF and DNA repair function. Conclusions: Secondary somatic mutations that restore BRCA1/2 in carcinomas with germline BRCA1/2 mutations predict resistance to platinum-based chemotherapy and PARP inhibitors, some strategies to reverse this type of drug resistance need further investigation.