Abstract
We aimed to characterize the somatic mutational landscape of oropharyngeal squamous cell carcinoma (OPSCC) and identify potential genomic drivers of tumor progression and therapeutic resistance using the AACR GENIE database.
Retrospective genomic analysis was employed.
We used publicly available data from the American Association for Cancer Research (AACR) Project GENIE database accessed via cBioPortal.
We analyzed 412 tumor samples from 401 patients diagnosed with OPSCC. Somatic mutations, clinical variables and tumor characteristics were extracted and analyzed. Statistical comparisons of mutation frequencies across gender and tumor stage (primary vs. metastatic) were conducted. Co-occurrence and mutual exclusivity analyses were performed to identify significant genomic patterns.
The most frequently mutated genes included
(30.1%),
(26.0%), and
(21.6%). Gender-specific analyses suggested potential enrichment of
and
mutations in females and of
in males. Distinct mutation patterns were observed between primary and metastatic tumors; primary tumors were enriched for mutations in
and
, while metastatic lesions harbored unique alterations in genes like
and
, suggesting pathways involved in immune evasion and chromosomal instability may drive disease progression. Co-occurrence was noted between
and
, and mutual exclusivity between
and
.
This study identifies distinct genomic signatures in OPSCC subgroups, highlighting candidate biomarkers in pathways like PI3K/AKT signaling that warrant further investigation. Validating these markers in prospective trials is a critical next step to translate these findings into personalized therapeutic strategies for OPSCC patients.