A new germline mutation in BRCA1 in a Chinese family with gynecologic cancers and colon cancer mimicking ovarian cancer: A case report

Abstract

BRCA1 is a key player in the homologous recombination DNA repair process. Pathogenic BRCA1 germline mutations confer a high risk of breast and ovarian cancers. Nevertheless, the association between BRCA1 mutations and colorectal cancer (CRC) risk remains unclear. While BRCA1 alterations significantly influence diagnosis and therapeutic decisions in breast and ovarian cancer, including the use of FDA-approved poly (ADP-ribose) polymerase (PARP) inhibitors, their role in CRC management is less established. Here, we present a case of a 57-year-old female diagnosed with CRC and a family history of ovarian and endometrial cancers. All her cancer-affected family members, including herself, were found to carry two germline BRCA1 mutations, including a novel mutation (c.212+2T>G) that has not previously been reported in CRC. The proband exhibited peculiar clinicopathological and molecular features, including a CK7-positive/CK20-negative immunophenotype that mimicked an ovarian origin. The patient received five cycles of nab-paclitaxel plus carboplatin, followed by maintenance therapy with the PARP inhibitor (PARPi) niraparib. This case provides real-world evidence supporting the pathogenicity of the BRCA1 c.212+2T>G mutation and highlights the potential of PARPi therapy in CRC patients harboring BRCA1 mutations. Further, it demonstrates the possibility of a rare immunohistochemical phenotype in CRC cells harboring a deleterious BRCA1 mutation.

Keywords

BRCA1 germline mutation / Colorectal cancer / Rare immunophenotype / Family history

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