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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1845-1853
NEOPLASIA
Lymphocyte predominance Hodgkin disease is characterized by
recurrent genomic imbalances
Sabine Franke,
Iwona Wlodarska,
Brigitte Maes,
Peter Vandenberghe,
Jan Delabie,
Anne Hagemeijer, and
Chris De
Wolf-Peeters
From the Center for Human Genetics, the Department of
Pathology, the Laboratory of Experimental Hematology, Catholic
University of Leuven, Belgium.
Single-cell polymerase chain reaction (PCR) has been used as a tool
to demonstrate clonality and B-cell origin of Reed-Sternberg (RS) cells
in Hodgkin disease (HD). An analogous approach was used to investigate
genomic imbalances in a (cyto)genetically poorly characterized
subentity: lymphocyte predominance Hodgkin disease (LPHD).
Nineteen cases of LPHD were selected for a comparative genomic
hybridization (CGH) study. CGH was performed with degenerate oligonucleotide primed-PCR (DOP-PCR)-amplified DNA from 4-5 microdissected CD20+ malignant cells. All analyzed cases
revealed a high number of genomic imbalances (average 10.8 per case),
involving all chromosomes but the excluded 19, 22, and Y, indicating a
high complexity of LPHD. The majority of detected aberrations were
recurrent. Gain of 1, 2q, 3, 4q, 5q, 6, 8q, 11q, 12q, and X, and loss
of chromosome 17 were identified in 36.8% to 68.4% of the analyzed
cases. Some of them have also been found in non-Hodgkin lymphoma (NHL),
and possibly represent secondary changes associated with disease
progression. Gain of 2q, 4q, 5q, 6, 11q, however, are much more rarely
observed in NHL and could be more specifically associated with LPHD.
Particularly interesting is a frequent overrepresentation of chromosome
arm 6q, a region usually deleted in NHL. Rearrangement of the
BCL6 gene (3q27) demonstrated by cytogenetics and
fluorescence in situ hybridization in 2 cases in this study suggests
its contribution in pathogenesis of LPHD. In conclusion, the data show
a consistent occurrence of genomic alterations in LPHD and highlight
genomic regions that might be relevant for development and/or
progression of this lymphoma entity.
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