Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations

Abstract

Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs. Results: A total of 183 GAs were found in 80 unique genes. High-grade tumors had more GAs (mean 5 ± 8) compared with low (2.3 ± 1.4) or intermediate (2.6 ± 1.5) (P = 0.019). TP53 GAs were seen in all tumor grades (41.7%) but were most common in high-grade malignancies (56%) (P=0.047). CDKN2A GAs were seen in 41.6% of tumors. PI3K/mTOR pathway activation, including PI3KCA mutations, were more common in high grade (52%) than in low- and intermediate-grade tumors (4.3%) (P=0.007). BAP1 GAs were observed in 20.8% of tumors and BRCA1/2 GAs present in 10.5% of specimens. ERBB2 amplifications were seen in only 8.3% of tumors. The TMB for this patient group was relatively low with only 5 (10%) of cases having greater than 10 mutations/megabase of sequenced DNA. Conclusion: CGP of salivary mucoepidermoid carcinomas revealed diverse GAs that may lead to customized treatment options for patients with these rare tumors.