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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-08-2482.
Submitted August 13, 2002
Accepted March 6, 2003
BCL6 gene translocation in follicular lymphoma: a harbinger of eventual transformation to diffuse aggressive lymphoma
Takashi Akasaka, Izidore S Lossos, and Ronald Levy*
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA, USA
* Corresponding author; email: levy{at}stanford.edu.
Follicular lymphoma (FL) is characterized by a relatively indolent clinical course, but the disease often transforms into a more aggressive large cell lymphoma with a rapidly progressive clinical course. In the present study, we analyzed 41 cases of FL known to have subsequently transformed to aggressive lymphoma and an additional 64 FL samples from patients not subsequently transformed. We studied BCL6 gene rearrangement by the methodology of long-distance inverse (LDI-)PCR. Of the 41 cases known to transform, sixteen (39.0%) harbored BCL6 translocation or deletion at the time of FL diagnosis. Among 64 cases not known to transform, BCL6 translocation was detected in nine (14.1%). The prevalence of BCL6 translocation in the group known to transform was significantly higher (P = .0048). Among the transformation cases, the partners of the BCL6 translocation were identified in 13 cases and included IGH, CIITA, U50HG, MBNL, GRHPR, LRMP, EIF4A2, RhoH/TTF, and LOC92656 (similar to NAPA), while in the control group the BCL6 partners were IGH, CIITA, SIAT1, and MBNL. In 13 cases paired specimens before and after transformation were available. Among these, a loss (three cases) or a gain (one case) of BCL6 translocation was observed after the transformation. Analysis of clonality showed that all of these cases represented the evolution of a subclone of the original tumor population. Our study demonstrated that BCL6 translocation is not necessary for transformation but that BCL6 translocation in FL may constitute a subgroup with a higher risk to transform into aggressive lymphoma.
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