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Histogenetic correlations between subcategories of small noncleaved cell
lymphomas
T Yano, JH van Krieken, IT Magrath, DL Longo, ES Jaffe and M Raffeld
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD
20892.
To assess the biologic relevance of the morphologic distinctions between
subtypes of small noncleaved cell lymphomas (SNCL), ie, the sporadic
Burkitt's type (sBT) and the non-Burkitt's type (nBT), we have examined the
molecular organization of several lymphomagenic oncogenes (c-myc, bcl-1,
bcl-2) and the potential pathogenetic contribution of the Epstein-Barr
virus (EBV). Twenty-nine cases of SNCL, not associated with
immunodeficiency syndromes, were reviewed and classified as sBT (18 cases)
or nBT (11 cases) without knowledge of the clinical or molecular data.
Southern blot analysis of 18 sBTs found 17 to contain c- myc
rearrangements. Fifteen of these comigrated with an Ig heavy-chain gene
segment, indicating t(8;14) translocation. Chromosome 8 breakpoints were
clustered in the first exon and the first intron of the c-myc gene.
Chromosome 14 breakpoints mapped to the JH locus in three tumors, the S mu
locus in nine tumors, and the S alpha locus in the remaining three tumors.
Cases involving the S alpha locus appeared to have a more rapid clinical
course. All sBTs possessed germline bcl-2 and bcl-1 gene fragments. In
contrast, Southern blot analysis of 11 nBTs found none with c-myc
rearrangements. Rather, three of 10 evaluable nBTs had bcl-2
rearrangements. The remaining seven showed no evidence of involvement by
any of the lymphoma-associated oncogene/breakpoint regions studied. EBV
genome was detected in two sBTs and in one nBT, and thus was not a
distinguishing feature. These results indicate that the subtle histologic
differences that distinguish subcategories of SNCL are significant
biologically and reflect distinct molecular mechanisms of lymphomagenesis.
Furthermore, the data suggest that the nBTs comprise a heterogeneous group
with respect to their molecular genetic composition and confirm the
remarkable molecular genetic homogeneity of the sBT group.
Volume 79,
Issue 5,
pp. 1282-1290,
03/01/1992
Copyright © 1992 by The American Society of Hematology
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