Whole exome sequencing of oral epithelial dysplasias reveals an association with new genes.. epithelial dysplasia

Background: The genetic basis of oralepithelial dysplasias is unknown and there is no reliable method of evaluating malignant transformation risk. We understand that somatic mutations are responsible for the transformation of the dysplastic mucosa to cancer. In addition, these genomic variations could represent objective markers to determine potential for malign transformation. Material and Methods: In the present study, We performed whole exome sequencing in ten samples of oral epithelial dysplasia of Brazilian and Chilean patients. Results:We identified 42 deleterious variants able to produce high impact changes in amino acid structures of 39 genes. Six new high impact variants were identified for the genes: FAM198B, CBWD5, PKD1L3, LRRC37A2, GAREM1 and GIPC1. Samples of high-grade epithelial dysplasia showed a tendency to accumulate more deleterious variants. Exclusive variants in genes was identified to low and high grade dysplasia groups. Considering variants shared by the two groups, the genes affected in most of the samples were: ACTN2, GLYCTK, TP53I11, WNK1, CELA1, OR6C1, SIX1, GABRG3, KRT24, MRPL27, and LAMA5. Variants in the OR6C1, GABRG3, KRT24, MRPL27 and LAMA5 genes, although present in some high grade dysplasia samples, were observed in low grade dysplasia group. Variants in the ACTN2, TP53I11, GLYCTK and CELA1 genes were present in all high grade dysplasia group. Conclusions: This study, with samples from a heterogeneous Latin America population and in-depth genomic evaluation method, allowed us to identified genes may be related to basal biological functions in oral epithelial dysplasias.