CGCI Non-Hodgkin Lymphoma (CGCI-NHL)
Program Description
The CGCI program includes comprehensive characterization of the genetic aberrations found in different pediatric and/or adult tumors. The CGCI-NHL study characterized B-cell non-Hodgkin lymphomas including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).
In combination, the lymphoid cancers (non-Hodgkin lymphoma, Hodgkin lymphoma, myeloma and chronic lymphocytic leukemia), constitute the fourth most common malignancy in both men and women in North America. Lymphomas typically have characteristic abnormal chromosomes, including translocations, indicating the relevance of mutations to how NHLs develop and behave. This project uses detailed analysis on a specific well-characterized set of tumors to provide a candidate list of genomic changes specific to and common across lymphoma types. The resulting data set will facilitate studies of clinical behavior, response to treatment, patient outcome and survival, and target pathways for therapeutic agents.
CGCI investigators probed genomic alterations more deeply than has been previously possible by using state-of-the-art RNA sequencing (mRNA-seq) and whole genome shotgun sequencing (WGS) coupled with leading edge bioinformatics, data management and analysis approaches. Specifically, 2nd-generation sequencing technologies were used to survey NHL for somatic mutations, chromosomal alterations and expression levels. Fresh-frozen biopsy material and constitutional DNA was assembled from uniformly staged, treated and followed NHL patients in British Columbia, Canada. The project sequenced tumor DNA and/or RNA from 117 NHL tumor samples and 10 cell lines. This includes the genomes or exomes of 1 Follicular Lymphoma (FL) and 13 diffuse large B-cell lymphoma (DLBCL) cases, all with matched constitutional DNA sequenced to comparable depths, RNA-sequencing (mRNA-seq) of 92 DLBCL, 12 FL and 8 B-cell NHL cases with other histologies and 10 DLBCL-derived cell lines. The DLBCL cases and cell-lines are from the two major subtypes of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC).
Publications
- Morin RD, Johnson NA, et al. (2010) Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010 Feb;42(2):181-5. (PMID: 20081860)
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View Publication Information And Supplementary Files - Morin RD, Mendez-Lago M, et al. (2011) Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. (PMID: 21796119)
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View Publication Information And Supplementary Files - Scott DW, Mungall KL, et al. (2012) TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood. 2012 May 24;119(21):4949-52. (PMID: 22496164)
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View Publication Information And Supplementary Files - Trinh DL, Scott DW, et al. (2013) Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood. 2013 May 2;121(18):3666-74. (PMID: 23460611)
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View Publication Information And Supplementary Files - Morin RD, Mungall K, et al. (2013) Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256-65. (PMID: 23699601)
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