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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-08-2577.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3681-3686
NEOPLASIA
Gains of 2p involving the REL locus correlate
with nuclear c-Rel protein accumulation in neoplastic cells of
classical Hodgkin lymphoma
Thomas F. E. Barth,
José I. Martin-Subero,
Stefan Joos,
Christiane K. Menz,
Cornelia Hasel,
Gunhild Mechtersheimer,
Reza M. Parwaresch,
Peter Lichter,
Reiner Siebert, and
Peter Möller
From the Abteilung für Pathologie des
Universitätsklinikums Ulm, Germany; Institut
für Humangenetik, Universitätsklinikum Schleswig-Holstein,
Campus Kiel, Germany; Deutsches Krebsforschungszentrum,
Abteilung Molekulare Genetik, Heidelberg, Germany;
Pathologisches Institut der Universität Heidelberg,
Germany; and Institut für Hämatopathologie,
Universitätsklinikum Schleswig-Holstein, Campus Kiel,
Germany.
Structural aberrations of the short arm of chromosome 2, mostly resulting in gains of 2p13~16, have recently been
described as being highly recurrent in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). As these gains consistently lead to increased copy numbers of the REL oncogene locus,
we investigated the expression of the c-Rel protein in a series of 30 cHL cases with known genomic REL status as determined by
comparative genomic hybridization and interphase cytogenetics.
Expression of the c-Rel protein was investigated in 26 biopsies by
immunohistochemistry. Distinct patterns were observed in HRS cells with
no staining, cytoplasmic, and/or nuclear staining for c-Rel. All 13 samples with additional copies of the REL locus displayed
nuclear staining for c-Rel, while 13 cHL samples lacking chromosome 2 (2p) gains displayed a significantly lower proportion or complete
absence of HRS cells with nuclear c-Rel expression. Detailed analysis using combined immunophenotyping and interphase cytogenetics of individual HRS cells demonstrated that REL gains correlated
with the presence of nuclear c-Rel staining. Additionally, in 2 cHL samples with translocation breakpoints in 2p13~16, nuclear staining of c-Rel was observed; in one of them the staining pattern was indicative of a truncated c-Rel protein. The correlation between structural aberrations involving the REL locus and nuclear
c-Rel accumulation in HRS cells qualifies REL as a
target gene of the frequent gains in 2p in cHL. The data suggest that
REL aberrations are a genetic mechanism contributing to
constitutive nuclear factor (NF)- B/Rel activation in cHL.
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