CGCI initiated the Non-Hodgkin Lymphoma Project to elucidate the mutation spectrums of the two most abundant forms of non-Hodgkin lymphoma (NHL)Opens in a New Tab: follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Though previous research uncovered some genetic abnormalities in FL and DLBCL, more extensive genome-wide analysis is needed to fully understand the biology of these two cancers.
NHL originates from the white blood cells of the immune system and is a common malignancy among North American adults. FL is an indolent (slow-growing) disease that derives exclusively from germinal center B-cells. A subset of FL transition into DLBCL, and the cause is yet unknown. Unlike FL, DLBCL is a fast-growing cancer that derives from either germinal center B-cells or activated B-cells.
By applying the most advanced sequencing analysis, CGCI researchers revealed frequent novel mutations in the chromatin modification pathway in subsets of NHL. Chromatin modification, which regulates gene expression, had not been previously implicated in NHL pathogenesis. Researchers are testing the functional significance of these chromatin modifying genes in driving the initiation and progression of NHL. Understanding the role of chromatin modification in NHL subpopulations may lead to better treatments for patients.
The NHL Project has completed all phases of the timeline.
This project is complete, and content will not change. Publications can be found here.
Visit the CGCI Overview page to learn more about the general timeline of CGCI projects.
Next generation sequencing technologies, including whole genome sequencing and RNA sequencing (mRNA-seq), are used to survey NHL tumors for somatic mutations, chromosomal alterations (e.g. translocations) and changes in gene expression. The tumor samples used for sequencing came from biopsies taken from NHL patients that were uniformly staged, treated and monitored in British Columbia, Canada.
As of 2012, investigators have accomplished the following sequencing analysis on NHL tumor samples as well as some experimental cell lines:
14 NHL tumors total (matched constitutional DNA sequenced to comparable depths)
- 13 DLBCL cases
- 1 FL case
Transcriptome Sequencing (mRNA-seq)
113 NHL tumors and 10 cell lines total
- 92 DLBCL cases
- 13 FL cases
- 8 B-cell NHL cases
- 10 DLBCL-derived cell lines (both germinal center B-cell (GCB) and activated B-cell (ABC) subtypes)
Data available through the CGCI Data Matrix and dbGaPOpens in a New Tab.