Burkitt Lymphoma Genome Sequencing Project (BLGSP): Introduction

• Published in: Blood 2016-12, Vol.128 (22), p.1760-1760
• Main Authors: Gerhard, Daniela S, Grande, Bruno, Griner, Nicholas, Casper, Corey, Gerdts, Sarah E., Omoding, Abraham, Orem, Jackson, Mbulaiteye, Sam M, Ogwang, Martin D., Reynolds, Steven J., Bhatia, Kishor, Ayers, Leona, Choi, John K, Mullighan, Charles G., Sandlund, John T., Alexander, Thomas B., Abramson, Jeremy S., Gross, Thomas G., Noy, Ariela, Bethony, Jeffrey, Leal, Fabio, Greiner, Timothy C, Jaffe, Elaine S., Harris, Nancy Lee, Gastier-Foster, Julie M., Bowen, Jay, Hanf, Benjamin, Schmitz, Roland, Martin, Jean-Paul, Martin, Marie-Reine, Irvin, John D., Miller, Ellen, Gesuwan, Patee, Hermida, Leandro C., Davidsen, Tanja M., Mungall, Andrew J., Ma, Yussanne, Marra, Marco A., Morin, Ryan D., Staudt, Louis M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1760.1760

Introduction: Burkitt Lymphoma (BL) is an aggressive B-cell lymphoma with a translocation involving MYC and immunoglobulin(Ig) loci. It is most common in children, but also affects adults, and occurs in sporadic, endemic and HIV-associated forms. The Epstein-Barr virus (EBV)-associated endemic subtype is the most common pediatric cancer in equatorial Africa, but also occurs in other parts of the world, for example in the rain forest of Brazil. Intensive chemotherapy is effective, but the associated toxicity requires supportive care that is not readily available in resource-poor regions. Previously published molecular characterization of small numbers of tumors indicated that the mutation profiles of endemic and sporadic cases are similar, but not identical. One goal of the BLGSP is to conduct comprehensive molecular characterization of BL by sequencing DNA and RNA from a large BL cohort - including endemic, sporadic, pediatric and adult cases - in order to define the genetic and phenotypic features that drive these cancers. These data will be analyzed with an intent toward developing new therapeutic strategies that can be deployed worldwide. Methods: The goal is to collect 160 BL cases, of which 50% will be endemic, 38% sporadic (pediatric and adult) and 12% from HIV+ patients. For the discovery phase, each tumor requires case-matching normal DNA as well as treatment, outcome and other clinical information. The optimal source of tumor DNA and RNA is from frozen tissue with at least 50% tumor nuclei, but FFPE immobilization is also accepted. Accrual locations include Africa, Brazil, Europe and the US. The BLGSP has developed extensive standard operating procedures for tissue collection, pathology review and tissue processing to reduce the variation associated with these parameters in the interpretation of the results (see https://ocg.cancer.gov/programs/cgci/projects/burkitt-lymphoma). The project also established procedures that allow sharing of all clinical and sample information through the National Cancer Institute Genomic Data Commons (https://gdc.cancer.gov). Molecular characterization includes whole genome sequencing of tumor and normal DNA (80X and 40X coverage, respectively), RNA-sequencing (RNA-seq) and micro-RNA sequencing. These data will enable the BLGSP to identify chromosomal rearrangements, chromosomal copy number alternations, somatic mutations (single nucleotide, insertions, deletions), viral insertions, expression signatures, viral expres