The goal of the Burkitt Lymphoma Genome Sequencing Project (BLGSP) is to explore genetic changes in patients with Burkitt lymphoma (BL) that could lead to better prevention, detection, and treatment of this rare and aggressive cancer. The Office of Cancer Genomics (OCG) at the National Cancer Institute (NCI) initiated BLGSP in collaboration with the Foundation for Burkitt Lymphoma Research. The molecular characterization data from Burkitt Lymphoma patients identified through BLGSP will be available to the research community worldwide in a publicly available, yet patient privacy-protected database.
Burkitt lymphoma is a type of non-Hodgkin lymphoma that occurs most often in children and young adults. It is associated with a chromosomal translocation of the MYC gene to one of the three immunoglobulin loci. BL is divided into three main clinical variants: endemic, sporadic, and immunodeficiency-associated. These variants are generally distinguishable by previous exposure to viral infection, tumor location, and geographic location of the patients, although there are exceptions. Current chemotherapy regimens are effective in approximately 40-90% of patients. Treatment success depends on age, stage of the disease, treatment regimen, and site of the treatment facility. The variability of tumor response demonstrates the need for new treatments to improve patient outcomes and quality of life.
BLGSP for pediatric cases has been completed. The publication from pediatric BL cases can be found here.
BLGSP for adult cases is an ongoing project that is currently in Phases I and II of the timeline.
Phase I: Document Development, Investigator Recruitment, Tissue Accrual
- Develop draft protocols, standard operating procedures, clinical report forms, data request form, investigator tracking form
- Identify and contact potential investigators at Tissue Source Sites
- Obtain Institutional Review Board approvals and institutional certification letters
- Verify Burkitt lymphoma diagnosis of each case by central pathology review of tissue
- Cancers that pass central pathology are submitted for processing into nucleic acids (if the frozen tissue or formalin-fixed, paraffin-embedded samples contain enough tumor nuclei), together with normal tissue, blood, or granulocytes, which are quality controlled
- Deposit clinical data into a project database
- Collect cases for validation phase
- Establish Working Groups
Phase II: Genome Sequencing and Analysis
- Complete genome and transcriptome sequencing
- Analyze sequence data for:
- Chromosome rearrangements and copy number alterations
- Expression profiles of mRNAs and non-coding RNAs (ncRNA), including any alternative spliced and fusion transcripts
- Identify somatic mutations in the genome and transcriptome and verify
- Investigate if RNA editing is activated
- Continue collecting cases for validation phase
Phase III: Validation of Findings
- Evaluate frequency of mutations in the validation cohort
- Analyze if or which clinical data correlate with the genetic changes
Phase IV: Publication
- Publish results in appropriate peer-reviewed journals
- Present results at scientific meetings, congresses, and symposia
Visit the CGCI Overview page to learn more about the general timeline of CGCI projects.
More information about BLGSP can be found on BLGSP Fact sheet.
BLGSP uses high-throughput genomic methods to develop a dataset of the spectrum of genetic alterations associated with all three variants of adult and pediatric BL. Tumor and normal tissues are collected from patients consented to participate in the project. BLGSP has accrued endemic, sporadic and immunodeficiency-associated Burkitt lymphoma tissues from many locations including sub-Saharan Africa, North America, Brazil and France.
Whole genome and transcriptome (mRNA and miRNA) sequencing will reveal somatic mutations, genomic rearrangements, copy number alterations, gene expression differences, fusion transcripts, and single-nucleotide polymorphisms (SNPs) for loss of heterozygosity. Associations between clinical parameters and genetic abnormalities will be discovered by integrating sequencing and pertinent clinical data. These discoveries will be used to develop more effective approaches to the diagnosis and treatment of BL.
See the Experimental Methods for the Burkitt Lymphoma Genome Sequencing Project page for detailed protocols.