Epigenetic IVD Tests for Personalized Precision Medicine in Cancer

Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved. Copyright © 2013 Elsevier Ltd. All rights reserved.

Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States.

Gliomas are the most common malignant primary brain tumors, of which glioblastoma is the most malignant form (WHO grade IV), and notorious for treatment resistance. Over the last decade mutations in epigenetic regulator genes have been identified as key drivers of subtypes of gliomas with distinct clinical features. Most characteristic are mutations in IDH1 or IDH2 in lower grade gliomas, and histone 3 mutations in pediatric high grade gliomas that are also associated with characteristic DNA methylation patterns. Furthermore, in adult glioblastoma patients epigenetic silencing of the DNA repair gene MGMT by promoter methylation is predictive for benefit from alkylating agent therapy. These epigenetic alterations are used as biomarkers and play a central role for classification of gliomas (WHO 2016) and treatment decisions. Here we review the pivotal role of epigenetic alterations in the etiology and biology of gliomas. We summarize the complex interactions between "driver" mutations, DNA methylation, histone post-translational modifications, and overall chromatin organization, and how they inform current efforts of testing epigenetic compounds and combinations in preclinical and clinical studies.