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.

Genome sequencing reveals molecular subgroups in oral epithelial dysplasia

Abstract This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

Epidermal Growth Factor Receptor (EGFR) is Overexpressed in Both Dysplasia and Neoplastic Oral Diseases

Introduction: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane cytoplasmic protein; studies indicate that it contributes to the development and progression of potentially malignant lesions to oral squamous cell carcinoma (OSCC). In the present study we determine and characterize the expression of EGFR in samples of oral epithelial dysplasia (OED) and OSCC. Materials and Methods: 54 samples with histopathological diagnosis of OED were selected, 19 of low grade dysplasia (LGD) and 35 of high grade dysplasia (HGD) and a tissue matrix was with 60 samples of OSCC and 9 of normal oral mucosa were used. EGFR detection was performed by immunohistochemical technique. In the photomicrographs, protein expression was deter- mined. Chi square test and Fisher test were used for statistical analysis (P <0.05). Results: 54% of OED and 60% of OSCC showed a significant pattern of high EGFR expression when compared with normal oral mucosa. Discussion: We found a tendency in LGD, HGD and OSCC to over expression of EGFR. Conclusion: There is over expression of EGFR in OED and OSCC, so it could be considered as an early marker of these patholo- gies