Sequence based analysis of U-2973, a cell line established from a double-hit B-cell lymphoma with concurrent MYC and BCL2 rearrangements

Abstract

BackgroundDouble-hit lymphoma is a complex and highly aggressive sub-type of B-cell lymphoma, which has recently been classified and is an area of active research interest due to the poor prognosis for patients with this disease. It is characterized by the presence of both an activating MYC chromosomal translocation and a simultaneous additional oncogenic translocation, often of the BCL2 gene. Recently, a cell line was established from a patient with this complex lymphoma and analyzed using conventional tools revealing it contains both MYC and BCL2 translocation events.FindingsIn this work, we reanalyzed the genome of the cell line using next generation whole genome sequencing technology in order to catalogue translocations, insertions and deletions which may contribute to the pathology of this lymphoma type.ConclusionsWe describe the cell line in much greater detail, and pinpoint the exact locations of the chromosomal breakpoints. We also find several rearrangements within cancer-associated genes, which were not found using conventional tools, suggesting that high throughput sequencing may reveal novel targets for therapy, which could be used concurrently with existing treatments.

Establishment and characterization of a novel MYC/BCL2 “double-hit” diffuse large B cell lymphoma cell line, RC

“…The CJ cell line that we established in 1990 before recognition of the clinical importance of DHL is believed to be the first DHL cell line showing both MYC and BCL2 gene rearrangements [ 8 ]. In 2003, we established another MYC/BCL2 DHL cell line, designated EJ-1, that morphologically resembled DLBCL [ 9 ], and recently, Hooper et al [ 10 ] described the establishment of a novel MYC/BCL2 DHL cell line, U-2973. Several recent studies indicate that the OCI-LY18, Sc-1, and CARNAVAL DLBCL cell lines also appear to demonstrate MYC/BCL2 double-hit characteristics [ 11 , 12 ], but a comprehensive genetic analysis of these cell lines has not been published.…”