Below are a few recent publications from our group. These papers highlight different aspects of our work and our general approaches. Many more papers are in the works.
The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.
Zhang J, Jima D, Moffitt AB, Liu Q, et al, Blood 2014.
Background/Inspiration Cancers are genetically heterogeneous with no two tumors showing exactly the same complement of mutations. However, the extent to which acquisition of mutations is driven by lineage remained poorly understood. In this study, we examined the epigenetic structure of normal B cells and its relationship to driver mutations occurring in lymphomas derived from those B cell types. Results and what they mean: We found that the epigenetic structure is closely linked to the genetic muations that occur in the corresponding lymphomas. This study indicates the close link between mutations and B cell lineage.
The landscape of genetic mutations in Burkitt lymphoma
Love et al, Nature Genetics 2012.
Background/Inspiration: Burkitt lymphoma is among the fastest growing tumors and is the most common pediatric cancer in Sub Saharan Africa. Sandeep first explored the patterns of gene expression in Burkitt lymphoma as a post-doctoral fellow (Dave et al, New England Journal of Medicine, 2006). Results and what they mean: We sequenced the first Burkitt lymphoma genome. That work alone recapitulates nearly 50 years of genetic studies in the disease. We also performed exome sequencing in 57 cases of Burkitt lymphoma to identify recurrent gene mutations in the disease. We found that ID3 mutations occurred in nearly a third of the cases and implicate this gene as a novel tumor-suppressor gene. We also found a number of other novel oncogenes.
Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs
Jima, Zhang et al, Blood 2010.
Background/Inspiration: We have depth perception because the visual fields from our two eyes have just enough in common and just enough that is not, that the brain is able to combine the two different images to add another dimension. We reasoned that sequencing microRNAs from the spectrum of normal and malignant cells that have just enough in common and just enough that is not, that we would be able to identify and validate microRNAs. Results and what they mean: We discovered over 200 new microRNAs in these normal and malignant cells. At the time of publication, this was one of the largest applications of deep sequencing for microRNA discovery.
Patterns of microRNA expression characterize stages of human B-cell differentiation
Zhang, Jima et al, Blood 2009.
Background/Inspiration: The role of microRNAs in different systems was a hot topic in 2007 when this project started. Results and what they mean: We characterized the expression of microRNAs in normal B cells for the first time and found that B cell stages can be differentiated based on their microRNA expression. We also demonstrated that these lineage-specific patterns are preserved in the corresponding lymphomas.