64P - Evaluating gene alterations associated with recurrence in oral cavity squamous cell carcinoma

Background

Oral cavity Squamous cell Carcinoma (OCSCC) is a heterogeneous group of malignancies with varying prognosis, overall survival, and reoccurrence rates. The advancement of comprehensive next generation sequencing has led to the discovery of potential biomarkers to further stratify these patients.

Methods

From electronic medical records, 80 patients with oral cavity squamous cell carcinoma were identified, 70 of the patients had complete multigene next generation sequencing (NGS) panels ranging from 200 genes for DNA and RNA sequencing to whole exome and full transcriptome sequencing. Treatment, response, recurrence, pathology, molecular characteristics, patient demographics were documented.

Results

Of the 70 HPV negative OCSCC, 15 patients were FAT1-positive (mean age at diagnosis: 66.5, F/M ratio: 7/8) and 55 patients were FAT1-negative (mean age at diagnosis: 59.7, F/M ratio: 28/27). Among the FAT1-positive patients, 13 (86%) had single FAT1 pathogenic and likely pathogenic mutation, 1 (7%) had FAT1 double mutation, and 1 (7%) had FAT1 loss. TP53 mutation rate did not vary with FAT1 mutation as was present at 13/15 (87%) in FAT1-positive patients and 47/55 (85%) in FAT1-negative patients. TERT mutation was more prevalent among FAT1-positive patients 12/15 (80%) than FAT1-negative patients 37/55 (67%). The rate of TP53 and TERT co-occurrence was higher in the FAT1-positive patients (73%), compared to the FAT1-negative (55%). Chromosome 11q copy number amplification was detected in 18/55 (33%) FAT-negative patients but only 2/15 (13%) FAT1-positive patients, suggesting a possible mutual exclusivity. FAT1-positive patients had improved overall survival (OS) of 55.7 months compared to FAT1-negative patients with OS of 47.5 months. While the rate of reoccurrence was similar (FAT1-positive 60%, FAT1-negative 65%), there was improved progression free survival (PFS) of 44.0 months compared to 37.15 months in FAT1-negative patients.

Conclusions

From this retrospective evaluation of a single institution, FAT1 mutation in OCSCC was associated with improved OS, PFS, higher rate of concurrent TERT mutations and lower rate of chromosome 11q copy application. Additional investigation into FAT-1 as a potential biomarker is warranted.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.