Detection of DNA methylation: Potential applications to diagnostic cytopathology

Inactivation of tumor suppressor genes is often the result of genetic mutations or deletions. However, another mechanism for silencing genes involves DNA methylation. In this setting, a methyl group is added to cytosine residues within the gene promoter region; that prevents transcription. Tumors usually contain multiple genes that have been silenced by methylation, unlike normal tissues, in which gene methylation events are less common. The list of genes methylated in a given tumor is often referred to as a gene methylation profile. Gene methylation profiles may be almost unique for each type of tumor. Methylation-specific polymerase chain reaction is a sensitive technique that can detect gene methylation in cytologic samples. Application of this technique to cytologic cancer screening tests may increase their sensitivity. Also, the introduction of novel chemotherapeutic drugs that target DNA methylation may utilize gene methylation assays on fine needle aspiration biopsies of tumors.