Mutational profiling of SMARCA4 and SMARCB1 in ampullary adenocarcinoma: a preliminary study

Dear Editor, Ampullary adenocarcinoma (AAC) accounts for only 0.2% of gastrointestinal malignancies and, although a surgical approach is suitable in 80% of cases, the 5-year survival rate is 30-50% with a high recurrence rate (50%) 1. The most frequent histological subtypes are mixed, pancreatobiliary (PB), and intestinal (INT) 1. Therapeutic approaches are limited, with approved gemcitabine-based regimen in PB and 5-fluororacil in INT AAC patients, respectively 1. AAC molecular profiling predominantly highlighted KRAS mutations followed by TP53, WNT/APC, PIK3CA, SMAD4 then BRAF, CDKN2A, FBXW7, ERBB2, PDFGRA, SMARCB1, RB1 1. Among them, only BRAF point mutations (detected in 9.3% of cases) and NTRK aberrant transcripts (2.0% of cases) make AAC patients eligible for Idabrafenib plus trametinib (MEK inhibitors) and anti NTRK inhibitors, respectively 1. In this scenario, the identification of novel specific molecular hallmark able to optimize the clinical management of AAC patients is crucial. SMARC proteins are core subunits of the SWI1/SNF1 complex and are involved in chromatin remodeling and DNA repair 2. SMARCA4 (BRAHMA RELATED GENE, BRG1), involved in ERBB, GnRH, and PI-3K/AKT/mTOR signaling pathways, acts in transcriptional modulation, DNA repair, and cell cycle checkpoint 2. A high expression level of SMARCA4 has been described as a negative prognostic factor across different solid tumors 2.