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TCF21 is a tumor suppressor gene which regulates mesenchymal cell transition into epithelial cells. It is frequently lost in human malignancies and is expressed in normal lung airway epithelial cells. It is silenced in the majority of head and neck squamous cell carcinomas and non-small-cell lung cancer tumor cells through a chemical change known as DNA methylation, a process that is potentially reversible.

The gene is located on chromosome 6, in region 6q23-q24.