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MYC rearrangements in histologically progressed follicular lymphomas
T Yano, ES Jaffe, DL Longo and M Raffeld
Laboratory of Pathology, Diagnosis and Centers, National Cancer Institute,
Bethesda, MD 20892.
Histologic transformation of low-grade follicular lymphoma to an
aggressive-grade lymphoma occurs in 60% to 80% of patients during their
clinical course. The events that drive the transformation process are
poorly understood. Deregulation of the MYC gene has been implicated in a
small number of cases. This observation led us to examine the molecular
organization of the MYC oncogene in 38 cases of histologically transformed
lymphomas that arose from follicular lymphomas, and in 18 of the initial
pretransformation follicular lymphomas. In addition, we examined 58
"control" low-grade follicular lymphomas that had not yet shown evidence of
histologic progression. Immunoglobulin heavy chain and light chain gene
rearrangements were detected in all biopsies and rearrangements of the
BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent
with their origin from follicular lymphomas), in 18 of 18 of the
pretransformation follicular lymphomas, and in 51 of 58 of the control
follicular lymphomas. All 18 pretransformation follicular lymphoma
specimens displayed at least one immunoglobulin gene and BCL-2
rearrangement in common with the corresponding histologically progressed
lymphoma, indicating a clonal relationship between the original follicular
lymphoma and the histologically transformed lymphoma. MYC rearrangements
were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%)
control follicular lymphomas. The latter MYC rearranged follicular lymphoma
was clinically aggressive and transformed to a high- grade lymphoma that
led to the death of the patient within 20 months. None of the 18
pretransformation follicular lymphomas showed MYC rearrangement, including
two from patients who later demonstrated MYC rearrangement in the
progressed aggressive lymphoma. PvuII mutational analysis failed to
identify additional MYC gene abnormalities in the progressed lymphomas.
Because the Epstein-Barr virus (EBV) is associated with a fraction of
high-grade lymphomas and is known to upregulate BCL-2, we looked for a
potential role for this agent in our progressed lymphomas. We did not
detect viral sequences in any case indicating that EBV does not play a
major role in progression. The presence of MYC rearrangements in a small
fraction of progressed aggressive lymphomas, and not in the corresponding
antecedent follicular lymphomas, suggests that acquisition of a MYC
rearrangement is in some cases associated with the transformation event.
Volume 80,
Issue 3,
pp. 758-767,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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