The lack of clinical biomarkers for head and neck cancer subtypes limits early diagnosis
and monitoring of disease progression. This study investigates genetic alterations
in clinically identical tumor, tumor-adjacent dysplastic epithelium (TADE) and normal
epithelium (NE) in five oral cancer patients to identify differences and commonalities
between oral cancer, TADE and NE. A VELscope®Vx device was used to identify
TADE and NE surrounding a clinical tumor for analysis of genetic alterations using the
OncoScan® assay. One of the tumor samples examined was an “M” class tumor with
a high confidence BRAF:p.G469A:c.1406G>C somatic mutation, which is the first to
be reported in oral cancer. Another tumor showed mosaicism in genetic alterations,
indicating the presence of multiple clones. Overall, each patient’s tumor, TADE and NE
showed a distinct genetic profile which indicates intertumoral clonal/genetic diversity.
Interestingly, four tumors showed gain of 3q26.2, 5q14.3, 8q24.3, 8q22.3, 14q32.33
and loss/LOH in 9p21.3 while all TADE had LOH on 22q11.23. In addition, some
genetic alterations progressed from NE through TADE into tumor in individual patients.
Furthermore, no molecular event was identified that is common to all NE and/or TADE
that progressed into tumor. This pilot study demonstrates the presence of genetic
heterogeneity in oral tumorigenesis, and suggests that there might exist some common
genetic alterations between tumors and TADE. However, this observation would need
to be further investigated and validated in a larger cohort of oral cancer patients for its
potential role in oral tumorigenesis.
ormal
epithelium
