Case Report: Co-Existence of BRCA2 and PALB2 Germline Mutations in Familial Prostate Cancer With Solitary Lung Metastasis.

BACKGROUND

Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.

METHODS

Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.

RESULTS

Two previously unreported germline mutations in the DDR pathway, (c.8474_8487delCATACCCTATACAG, p.A2825Vfs15) and (c.472delC, p.Q158Rfs19) were identified in a patient with metastatic PCa. A specific therapeutic regimen including androgen deprivation therapy, locally radical radiotherapy, and systemic platinum chemotherapy worked well against his cancer. In addition, the metastatic ovarian cancer in the proband's half-sister harboring the same germline mutation also responded well to platinum chemotherapy.

CONCLUSIONS

The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.