Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations.
We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas.



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.



A total of 183 GAs were found in 80 unique genes. High-grade tumors had more GAs (mean 5 ± 3.8) 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.



CGP of salivary mucoepidermoid carcinomas revealed diverse GAs that may lead to customized treatment options for patients with these rare tumors.
Foundation Medicine, Inc., Cambridge, USA.|Center for Precision Medicine, Zhejiang University International Hospital, Hangzhou, Zhejiang, China.
K
K
Wang
Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
J D
JD
McDermott
Foundation Medicine, Inc., Cambridge, USA.
A B
AB
Schrock
Foundation Medicine, Inc., Cambridge, USA.
J A
JA
Elvin
Foundation Medicine, Inc., Cambridge, USA.
L
L
Gay
Departments of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
S D
SD
Karam
Departments of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
D
D
Raben
Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA.
H
H
Somerset
Foundation Medicine, Inc., Cambridge, USA.
S M
SM
Ali
Foundation Medicine, Inc., Cambridge, USA.|Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, USA.
J S
JS
Ross
Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA.
D W
DW
Bowles
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D043222:Ubiquitin Thiolesterase
BAP1; PI3K; genomic alteration; head and neck cancer; mucoepidermoid carcinoma; salivary gland cancer