Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes

Abstract

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy

“…In our study, we observed EGFR overexpression in 56.3% of cases, and we also showed that high EGFR expression tends to be associated with tumors with grade III of malignancy. This aligns with research in human oral [65][66][67] and cutaneous squamous cell carcinomas [68]. The association between EGFR immunoexpression and the degree of malignancy is also consistent with previous studies on several canine cancer [69,70].…”

New insights into the role of the oral leukoplakia microenvironment in malignant transformation

“…Changes in some genes have been identified in oral epithelial dysplasia that may contribute to modifications in the tumor microenvironment of leukoplakia, such as in FAM198B ( 56 ). A positive correlation has been determined between FAM198B and the infiltration of major immune cells (including macrophages, Treg, and NK cells), and this gene has been suggested as a promising therapeutic target to reverse gastric cancer ( 57 ).…”

“…Understanding their interactions with dysplastic cells, such as antigen presentation or immune suppression, is critical to unraveling the early events in oral cancer development and holds promise for improved diagnostic approaches. Changes in some genes have been identified in oral epithelial dysplasia that may contribute to modifications in the tumor microenvironment of leukoplakia, such as in FAM198B (56). A positive correlation has been determined between FAM198B and the infiltration of major immune cells (including macrophages, Treg, and NK cells), and this gene has been suggested as a promising therapeutic target to reverse gastric cancer (57).…”