Aberrant Gene Silencing in Tumor Progression: Implications for Control of Cancer

Abstract

Although it is clear that genetic alterations are critical for the initiation and maintenance of human cancer, it is also becomingevident that epigenetic changes may be essential for the development of these diseases as well. The best studied of theselatter processes is heritable transcriptional repression of genes associated with aberrant DNA hypermethylation of their promoters.Herein we review how very early occurrence of these gene silencing events may contribute to loss of key gene functionswhich result in disruption of cell regulatory pathways that may contribute to abnormal cell population expansion. Thesealtered regulatory events may then provide a setting where mutations in the same disrupted pathways may be readily selectedand serve to lock tumor progression into place. This hypothesis has potential impact on means to prevent and control cancerand for the use of epigenetic markers for cancer risk assessment and early diagnosis.