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TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma
May 24, 2012

Using RNA sequencing (RNA-seq), Scott et al. discovered a novel recurrent gene fusion between TBL1XR1 and TP63 in diffuse large B-cell lymphoma (DLBCL). Further analysis revealed the TBL1XR1/TP63 fusion was exclusive to DLBCL derived from germinal center B-cells. TBL1XR1 encodes a component of the NCoR/SMRT transcription repressor complex, and TP63 encodes a protein that is part of the TP53 family of transcription factors. These results demonstrate how RNA-seq is helping to reveal previously unidentified gene fusions in various cancers.

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
July 27, 2011

In a recent Nature article, Morin et al. uncovered a novel role for chromatin modification in driving the progression of two non-Hodgkin lymphomas (NHLs), follicular lymphoma and diffuse large B-cell lymphoma. Through DNA and RNA sequencing of 117 tumor samples and 10 assorted cell lines, the authors identified and validated 109 genes with multiple mutations in these B-cell NHLs. Of the 109 genes, several genes not previously linked to lymphoma demonstrated positive selection for mutation including two genes involved in histone modification, MLL2 and MEF2B. MLL2 emerged as a major tumor suppressor gene in both cancers, whereas, MEF2B appears restricted to lymphomas derived from germinal center B-cells. Their data provide potential therapeutic targets for NHL patients.

The Genetic Landscape of the Childhood Cancer Medulloblastoma
December 16, 2010

Through whole exome sequencing, researchers have found that pediatric medulloblastoma, the most common malignant brain tumor found in children, contains a fraction of the mutations found in adult cancers. These findings, reported in the December 16 issue of Science, reveal that mutations of genes involved in normal developmental processes occur with greater frequency in medulloblastoma tumors.

Somatic mutation of EZH2 (Y641) in Follicular and Diffuse Large B-cell Lymphomas of Germinal Center Origin
Nature Genetics
January 17, 2010 as an Epub ahead of print

Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays. Together, these results highlight a conserved biologic pathway important for DLBCL and FL pathogenesis.