There’s no denying that epigenetics and cancer are intimately intertwined, and that untangling this connection is vitally important in expanding our understanding of cancer initiation and development. Epigenetic signals are reversible regulators of gene expression and as such, make compelling targets in the study and treatment of cancer.
As high-throughput data analysis becomes the norm, entire panels of cancer genomes can be evaluated at once. Recent next-gen sequencing of cancer patient samples revealed recurrent mutations in chromatin mediated signaling genes. Here, authors Shah, Denton and others took this approach a step further – screening tumor samples for mutations and altered expression across 441 genes related to chromatin-mediated signaling factors. Using this approach, they were able to tease out new information regarding the link between cancer and mutated chromatin factors, and corroborate previously published work.
The researchers analyzed mutational and transcriptional data from TCGA and the ICGC and from this found:
- In tumor samples, chromatin factors are more likely to be mutated compared to random genes, but less likely to have altered gene expression.
- Chromatin factors were largely defined by a tumor suppressor pattern of mutations – meaning the mutations are spread throughout the gene. Oncogenes are characterized by mutational hotspots on a gene, and several previously unpublished hotspots were identified.
- Chromatin factor mutations in cancer trend towards altering cell replication via links between histone methylation and replication machinery, and affecting genomic instability by means of telomere lengthening or impeding double-strand break repair.
- In most cases, overexpression of a particular gene does not correlate with an increase in copy number, which indicates passenger mutations in cancer.
Analysis of 441 genes related to chromatin signaling has allowed for identification of numerous genes, hotspots and mutations in epigenetic machinery in a variety of tumor types, helping to further unwind the link between epigenetics and cancer. Think the gene you study might be one of them? Find out in Epigenetics & Chromatin, December 2014.