Journal
NEUROTHERAPEUTICS
Volume 6, Issue 3, Pages 436-446Publisher
SPRINGER
DOI: 10.1016/j.nurt.2009.04.002
Keywords
Genomics; epigenomics; gliomas; methylation; acetylation
Funding
- National Brain Tumor Society
- Accelerated Brain Cancer Cure
- Goldhirsh Foundation
- Karen Osney Brownstein Endowed Chair
- NIH Institutional Research Service Award in Molecular and Cellular Mechanisms in Cancer
Ask authors/readers for more resources
Gliomas arise through genetic and epigenetic alterations of normal brain cells, although the exact cell of origin for each glioma subtype is unknown. The alteration-induced changes in gene expression and protein function allow uncontrolled cell division, tumor expansion, and infiltration into surrounding normal brain parenchyma. The genetic and epigenetic alterations are tumor subtype and tumor-grade specific. Particular alterations predict tumor aggressiveness, tumor response to therapy, and patient survival. Genetic alterations include deletion, gain, amplification, mutation, and translocation, which result in oncogene activation and tumor suppressor gene inactivation, or in some instances the alterations may simply be a consequence of tumorigenesis. Epigenetic alterations in brain tumors include CpG island hypermethylation associated with tumor suppressor gene silencing, gene-specific hypomethylation associated with aberrant gene activation, and genome-wide hypomethylation potentially leading to loss of imprinting, chromosomal instability, and cellular hyperproliferation. Other epigenetic alterations, such as changes in the position of histone variants and changes in histone modifications are also likely to be important in the molecular pathology of brain tumors. Given that histone deacetylases are targets for drugs that are already in clinical trial, surprisingly little is known about histone acetylation in primary brain tumors. Although a majority of epigenetic alterations are independent of genetic alterations, there is interaction on specific genes, signaling pathways and within chromosomal domains. Next-generation sequencing technology is now the method of choice for genomic and epigenome profiling, allowing more comprehensive understanding of genetic and epigenetic contributions to tumorigenesis in the brain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available