Clonal cytogenetic abnormalities in Hodgkin's disease

Abstract

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non-Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent cytogenetic picture of HD. Over a 6 1/2-year period, we received 95 specimens of HD for cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81%) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte-depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near-tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q13),del(6)(q23),i(6p). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1p, 1q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki-1-positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

“…26 Using probes specific for the centromeric region and the long arm of the chromosome 6, we found that one case showed a pattern highly suggestive for the presence of an isochromosome 6p. This aberration is very common in human retinoblastoma, 27 but has also been reported in approximately 1% of acute lymphoblastic leukemia 28 and Hodgkin's lymphoma 29 and in 6% of primary mediastinal 30 and gastric NHLs, 25 as well as in individual cases of follicular, 10 nodal diffuse large B-cell 31 and nasal T/NK NHLs 32 and of Waldenstrom's macroglobulinemia. 33 It has been suggested that, similarly to cyclin D1 in mantle cell lymphoma and plasma cell myeloma, cyclin D3 may be deregulated in hematopoietic disorders as a consequence of the t(6;14) translocation.…”

Karyotypic dissection of Hodgkin's disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification

“…ASA rearrangements together comprise by far the most numerous breakpoints reported in HD, [33][34][35][36][37][38][39][40][41][42][43][44] in particular those anaLeukemia lyzed before treatment, 40 implying a spontaneous origin rather than via therapeutic induction. Ectopic rDNA has been noted previously in the L-540 HD cell line 61 which, as reported in this study (Table 2), may be a more general feature of HD cell lines.…”

“…In contrast to ASA (p11-p13) breakpoints, there is no excess of centromeric (p10/q10) rearrangements in HD [33][34][35][36][37][38][39][40][41][42][43][44] to indicate targeting any of the several families of resident DNA repeats, notably ␣-sat. DNA.…”

Investigation of miR9-1, miR9-2 and miR9-3 Methylation in Hodgkin Lymphoma

“…This observation suggests that miR9-2, located on 5q14.3, is the main locus affected in HL. Previous reports support this observation; indeed, earlier cytogenetic studies showed that the 5q chromosome is frequently altered in various types of hematological malignancies, including leukemia [33,34], non-HL [35,36] and HL [37]. It has been shown that the long arm of chromosome 5 harbors a large number of genes coding for hematopoietic growth factors or their receptors [38].…”