Molecular epigenetics and genetics in neuro-oncology
Nagarajan RP et al. - In a review of molecular epigenetics and genetics in neuro-oncology, it was concluded that 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 the method of choice for genomic and epigenome profiling, allowing more comprehensive understanding of genetic and epigenetic contributions to tumorigenesis in the brain. Methods- Gliomas arise through genetic and epigenetic alterations of normal brain cells, although the exact cell of origin for each glioma subtype is unknown.
- Alteration-induced changes in gene expression and protein function allow uncontrolled cell division, tumor expansion, and infiltration into surrounding normal brain parenchyma.
- Genetic and epigenetic alterations are tumor subtype and tumor-grade specific.
Results- Particular alterations predict tumor aggressiveness, tumor response to therapy, and pt 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 position of histone variants and changes in histone modifications are also important in 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.
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