Abstract

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.

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Authors

Paola Parente - Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy

Francesco Pepe - Department of Public Health, Federico II University of Naples, Naples, Italy

Claudia Covellu - Pathology Unit, Ospedale Desenzano del Garda, Italy

Gianluca Russo - Department of Public Health, Federico II University of Naples, Naples, Italy

Federica Russo - Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy

Giancarlo Troncone - Department of Public Health, Federico II University of Naples, Naples, Italy

Paolo Graziano - Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

Umberto Malapelle - Department of Public Health, Federico II University of Naples, Naples, Italy

How to Cite
Parente, P., Pepe, F. ., Covellu, C., Russo, G., Russo, F., Troncone, G., Graziano, P., & Malapelle, U. (2024). Mutational profiling of SMARCA4 and SMARCB1 in ampullary adenocarcinoma: a preliminary study. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 116(5). https://doi.org/10.32074/1591-951X-1028
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