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 L1904fs*5 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 pL1908fs*2 mutation, indicating its location in the cis position on the same allele as the germline mutation. The pL1908fs*2 deletion, alongside the original L1904fs*5, 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.