Cytogenetic analysis of 147 cases of non‐Hodgkin's lymphoma: non‐random chromosomal abnormalities and histological correlations

Abstract

A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease.

Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma

“…[26][27][28][29][30][31] In some studies, changes such as trisomies of chromosomes 2/2p, 3/3p, 5, 6, or 18, monosomy 7, del(6q), abnormalities of 17 [Ϫ17, del(17p), i(17q)], and breaks or duplications of 1q have been shown to correlate with advanced stage disease and poor prognosis. 13,19,[32][33][34][35][36] In the present study, SKY analysis identified 3 sites (2q31, 3q27, 7q22) that significantly associated with advanced-stage disease or poor treatment response. Two of these, 2q31 and 7q22, have previously not been described by G-banding studies.…”

“…The types of chromosomal rearrangements are diverse and include translocations, deletions, duplications, and several undefined aberrations such as additions and marker chromosomes. 4,12,[18][19][20][21] This study is the first reported to use SKY to fully characterize the chromosomal rearrangements in a panel of histologically reconfirmed DLBCL. In more than 90% of the cases, SKY provided additional cytogenetic information.…”

“…The frequency of 10 other recurring translocation breakpoints (1p11-13, 2p13, 2q31, 3p21, 7q11, 7q22, 12q11-13, 15q13-15, 17q11-21, 22q11) was higher in SKY analysis compared with G-banding (11%-17% vs 1%-5%). 4,12,[18][19][20] Based on G-banding analysis, we have previously shown that translocations involving 14q32 and 3q27 were the most frequent and together affected 50% of cases. Among these, the partner chromosomes involved remained unidentified in 5% to 15% of the cases due to poor morphology or karyotype complexity.…”

Identification of a novel cDNA, encoding a cytoskeletal associated protein, differentially expressed in diffuse large B cell lymphomas

“…These data suggest that LB1 expression might be related to morphologic characteristics of lymphomatous cells, which could re¯ect the B lymphocyte dierentiation stage aected by the neoplastic process, or other illde®ned cellular processes associated with these particular morphologic aspects. Interestingly, the LB1 gene was mapped to chromosome 13 at band q14, a region that is rearranged by translocations or interstitial deletions in about 10% DLBL (Juneja et al, 1990;Whang-Peng et al, 1995 and Chritian Bastard, personal communication). As LB1 is highly expressed in some lymphoid tissues and deregulated in DLBL, it is tempting to speculate that it might be involved in the reorganization of the cytoskeleton associated with lymphocyte polarization, mobility, or signalling pathways initiated by the activation of adhesion, cytokine or antigen receptors (Gomez et al, 1997;Juglo and Jongstra-Bilen, 1997;Lub et al, 1997;Manie et al, 1997).…”

Gene expression profiling of follicular lymphoma and normal germinal center B cells using cDNA arrays

“…by guest www.bloodjournal.org From abnormalities have been described in FL. [66][67][68][69][70][71][72] Additional chromosomal abnormalities involving, for example, p53, play a central role in the progression of FL. These additional abnormalities are likely to be important in the development of the disease, because Bcl-2/IgH is necessary but not sufficient for tumor development.…”