High likelihood of BRCA2 reversion mutation in pancreatic cancer post-platinum-based chemotherapy: a case study.

A 54-year-old man with resectable pancreatic cancer and abnormally high levels of carbohydrate antigen 19-9 (CA19-9) underwent 6 months of platinum-based chemotherapy. This treatment substantially reduced the primary tumor size and normalized CA19-9 levels. Subsequently, radical surgery was conducted. However, eight months post-surgery, CA19-9 levels re-elevated, and lymph-node recurrence was observed. The patient underwent treatment with poly(adenosine diphosphate ribose) polymerase inhibitors (PARPi) following the detection of frameshift L1904fs5 via BRACAnalysis CDx. This mutation revealed a stop codon, leading to the inactivation of the function. Additionally, the patient tested positive for a mutation in the breast cancer susceptibility gene 2 (). Two months after starting PARPi, there was evidence of tumor shrinkage. Nevertheless, 5 months later, CA19-9 levels increased again, and new metastatic tumors in the liver were identified. Genomic profiling test (FoundationOne CDx) of surgically resected specimens revealed a pL1908fs2 mutation, indicating its location in the cis position on the same allele as the germline mutation. The pL1908fs2 deletion, alongside the original L1904fs5, resulted in three deletions, equating to one amino acid deletion. This deletion ultimately reversed the stop codon, leading to the restoration of functionality. Despite treatment with PARPi for postoperative recurrence, a sustained response was not achieved owing to reversion mutations. It is essential to acknowledge the rarity of reversion mutations, which limit the effectiveness of PARPi.