They say it’s the quiet ones that you have to watch out for. Canadian researchers may have had that in mind when they pondered the genetic causes of non-Hodgkin lymphoma (NHL). Through some extra digging (and sequencing), they uncovered several mutant genes that had remained hidden until now, including some that have roles in histone methylation and acetylation.
To better understand NHL, the Canadian scientists sequenced genomes of tumor and normal tissue samples from patients and found 651 genes with coding single nucleotide variants—and only 25 of these were known cancer genes. Then, the researchers sequenced RNA (RNA-seq) from the samples and discovered that 109 genes had at least two somatic mutations in them. Many of these genes are involved in lymphocyte activation, lymphocyte differentiation, and apoptosis, but others are epigenetic players. A closer look at the epigenetic genes revealed:
- MLL2, an H3K4-specific methyltransferase, is a major tumor suppressor gene in NHL. About half of the NHL samples that they sequenced had two MLL2 mutations. Reports show that mutations in MLL2 are linked to some cancers, and now these data implicate MLL2 in NHL. The MLL2 mutations were mostly of the loss-of-function variety.
- Mutations in MEF2B, a gene that encodes a transcription factor that recruits histone acetylation and deacetylation enzymes, were also common. These mutations were usually non-synonymous amino acid substitutions.
Check out all the hidden mutant genes that were found at Nature, July 2011.