Molecular overview of major salivary gland carcinomas in chilean patients: 2 case reports

Abstract

Abstract Background Salivary gland tumors (SGTs) are rare neoplasms that account for 8.5 % of head and neck cancers and comprise a highly heterogeneous group of benign and malignant subtypes, according to the World Health Organization. In Chile, epidemiological and molecular data are limited, and comprehensive genomic profiling has rarely been reported. Within our institutional head and neck cancer registry, two patients with malignant major salivary gland carcinomas were identified, each exhibiting distinct molecular profile. Case presentation The first case demonstrated that genomic analysis identified two gene fusions. BRAF -driven profile characterized by a dominant BRAF (p.V600E), including TRIM24–BRAF and SDHC-RPA1 rearrangements. These findings suggest that MAPK pathway activation, mitochondrial dysfunction, and replication stress occur within a cooperative evolutionary framework. Genomic profiling of the second patient revealed three fusion events, one of which was a fusion-driven tumor dominated by FGFR2-ETV6 rearrangement. A secondary fusion, AFG1L-ATF6B was identified, accompanied by TP53 alterations and a third intergenic FGFR2 rearrangement. This profile indicates structural complexity and a strong dependency on FGFR2 signaling, with additional secondary alterations affecting genes involved in growth signaling and in epigenetic regulation. Conclusions Integrated clinical-molecular analysis revealed a hierarchical organization with dominant driver events and multiple cooperative alterations. These findings highlight the molecular diversity of SGTs and support genomic profiling to identify actionable targets, particularly FGFR2, enabling precision oncology approaches in Chilean patients.