Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances.
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.
Center for Human Genetics, the Department of Pathology, the Laboratory of Experimental Hematology, Catholic University of Leuven, Belgium.
S
S
Franke
I
I
Wlodarska
B
B
Maes
P
P
Vandenberghe
J
J
Delabie
A
A
Hagemeijer
C
C
De Wolf-Peeters
D000328:Adult; D000368:Aged; D018951:Antigens, CD20; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018929:Cell Culture Techniques; D002648:Child; D002869:Chromosome Aberrations / Q000175:diagnosis* / Q000235:genetics; D025063:Chromosome Disorders; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005629:Frozen Sections; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
D018951:Antigens, CD20; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors