Genes acting as cancer “drivers” across multiple malignancies revealed

A pan-cancer and multi-omics study led by scientists from the International Agency for Research on Cancer (IARC) has revealed that epigenetic regulator genes, when disrupted through genetic or non-genetic mechanisms, may act as drivers (“epidrivers”) in cancer development and have impacts on cancer cell phenotype. These findings were published today in the journal Genome Research.

Epigenetic regulator genes are a group of more than 400 coding genes in the human genome, most of which encode enzymes that add (“writers”), modify or revert (“editors”), or recognize (“readers”) epigenetic modifications that control a range of critical cellular processes. Based on the observation that many epigenetic regulator genes are frequently disrupted across different malignancies, they are candidates to be drivers of cancer development and progression, potentially acting as oncogenes or tumour suppressor genes.

The pan-cancer and multi-omics analysis revealed that, in addition to mutations, copy number alterations in epigenetic regulator genes were more frequent than previously anticipated and tightly linked to expression aberrations. The study also revealed epidrivers within and across malignancies with shared driver mechanisms, operating across multiple cancer types, that confer the hallmarks of cancer (such as genome instability, evading growth suppressors, enabling replicative immortality, and activating invasion and metastasis).

Halaburkova A, Cahais V, Novoloaca A, Gomes de Silva Araujo M, Khoueiry R, Ghantous A, Herceg Z
Pan-cancer multi-omics analysis and orthogonal experimental assessment of epigenetic driver genes
Genome Res, Published online 22 September 2020;
https://doi.org/10.1101/gr.268292.120

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