Histone-modifying genes are frequently mutated in non-Hodgkin's lymphoma (NHL), finds a study published online in Nature.

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) represent two of the most common non-Hodgkin lymphomas.

FL is indolent and typically incurable disease characterised by clinical and genetic heterogeneity; while DLBCL is aggressive but comprises at least two distinct subtypes that respond to treatment.

Current knowledge of the specific genetic events resulting in DLBCL and FL has been limited to the presence of a few recurrent genetic abnormalities.

In the study Marco Marra and colleagues from BC Cancer Agency (Vancouver, Canada) sequenced both tumour and matched normal DNA from 13 patients with DLBCL and one patient with FL to identify genes with mutations.

The team also undertook RNA sequencing analysis from these patients and another 113 patients with NHL.

Altogether the team identified 109 genes with clear evidence of somatic mutation in multiple individuals. Most notably genes with roles in histone modifications were frequent targets of somatic mutation.

For example, 32% of DLBCL and 89% of FL cases, respectively, had somatic mutations in MLLs, which encodes a histone methyltransferase; and 11.4% and, 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Histone proteins act as spools for nuclear DNA to wrap around and their modification is known to influence gene expression.

"Our data indicate that post-transcriptional modification of histones is of key importance in germinal centre B cells and deregulated histone modification due to these mutations is likely to result in reduced acetylation and enhanced methylation, and acts as a core driver event in the development of NHL," write the authors, adding that to the best of their knowledge, the majority of these genes had not previously been associated with any cancer type.

Article: R D Morin, M Mendez-Lago, AJ Mungall, et al. Frequent mutation of histone modifying genes in non-Hodgkin lymphoma. Nature. Doi:10.1038/nature10351.