Loss of EphA7 Expression in Basal Cell Carcinoma by Hypermethylation of CpG Islands in the Promoter Region

Abstract

Basal cell carcinoma (BCC) is the most common malignancy worldwide, with increasing incidence. BCCs present low mortality but high morbidity, and its pathogenesis remains unclear. Eph receptors have been implicated in tumorigenesis. EphA7 plays a role as a tumor suppressor in certain cancers. We checked EphA7 expression levels and methylation status in a set of BCCs, benign skin diseases, and compound nevus tissue samples using immunohistochemistry. EphA7 protein was positively expressed in normal basal cells, benign skin diseases, and compound nevus cells, but lost in areas of BCC tissues. We detected hypermethylation in BCC tissue samples with reduced expression of EphA7. There is a significant relationship between the expression level of EphA7 receptor protein and the methylation status of CpG islands in the EphA7 promoter region ( P < 0.001 ). To our knowledge, this is the first study to report the EphA7 expression profile and hypermethylation of EphA7 in BCC. The role of the EphA7 gene and the status of hypermethylation in tumorigenesis and treatment of BCC warrant further investigation.

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation

“…Mutations of the PTCH hallmark gene are detected in 50%–60% of BCCs, and PTCH promoter methylation is at a lower level (31%) 13 . Loss of p53‐regulated 14‐3‐3sigma gene expression due to hypermethylation has also been observed in BCC, 14 and previously reported EphA7 expression loss and promoter hypermethylation in BCC 15 …”

“…13 Loss of p53-regulated 14-3-3sigma gene expression due to hypermethylation has also been observed in BCC, 14 and previously reported EphA7 expression loss and promoter hypermethylation in BCC. 15 Rho family GTPases have been implicated in many aspects of tumorigenesis, acting as key regulators of various cell functions, including cytoskeleton organization, migration, gene transcription, adhesion, proliferation and survival. Rho proteins function as molecular switches, with an active GTP-bound form and an inactive GDPbound form.…”