Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia

Escudier, Susan; Pereira-Leahy, JM; Drach, JW; Weier, Heinz-Ulrich; Goodacre, AM; Cork, MA; Trujillo, JM; Keating, MJ; Andreeff, M.

doi:10.1182/blood.v81.10.2702.bloodjournal81102702

Cited by 12 publications

(21 citation statements)

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“…In all studies that compared conventional chromosome banding techniques and interphase cytogenetics, the frequency of trisomy 12 was higher when assessed by FISH using DNA probes that recognized the repetitive sequences of the cen-tromeric and pericentromeric region. The frequencies of trisomy 12 in the FISH studies range from 10 to 20% in most European series, to more than 30% in two studies from the United States (86,88). This variation possibly results from patient selection; however, differences may also be due to a different geographical distribution of this chromosome aberration.…”

Section: Clinical Impact Of 11q22-q23 Deletion In Cllmentioning

confidence: 94%

“…Using restriction fragment length polymorphism (RFLP) studies, it was shown that trisomy 12 in CLL results from duplication of one homolog, rather than from loss of one homolog, and triplication of the remaining one (84). Trisomy 12 is the aberration most extensively studied by molecular cytogenetics in CLL (8,62,(85)(86)(87)(88)(89)(90)(91) (Table 1). In all studies that compared conventional chromosome banding techniques and interphase cytogenetics, the frequency of trisomy 12 was higher when assessed by FISH using DNA probes that recognized the repetitive sequences of the cen-tromeric and pericentromeric region.…”

Section: Clinical Impact Of 11q22-q23 Deletion In Cllmentioning

confidence: 99%

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Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Stilgenbauer

Lichter

Döhner

2000

Rev Clin Exp Hematol

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The genetic features of B-cell chronic lymphocytic leukemia (CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis. Using FISH, the detection of chromosomal aberrations can be performed at the single cell level in both dividing and non-dividing cells, thus circumventing the need of metaphase preparations from tumor cells. Probes for the detection of trisomies, deletions and translocation breakpoints can be applied to the regions of interest with the growing number of clones available from genome-wide libraries. Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations. However, for the other frequently affected genomic regions, the search for candidate genes is ongoing. In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival. In addition, deletion 17p has been associated with resistance to treatment with purine analogs. Therefore, genetic abnormalities may allow a risk assessment for individual patients at the time of diagnosis, thus giving the opportunity for a risk-adapted management.

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Section: Clinical Impact Of 11q22-q23 Deletion In Cllmentioning

confidence: 94%

Section: Clinical Impact Of 11q22-q23 Deletion In Cllmentioning

confidence: 99%

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Stilgenbauer

Lichter

Döhner

2000

Rev Clin Exp Hematol

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“…Our group and others have reported on numerical chromosome 12 abnormalities in chronic lymphocytic leukemia by using FISH (Perez-Losada et al, 1991;Anastasi et al, 1992;Cuneo et al, 1992;Qumsiyeh I 62 rourm ET AL. Escudier et al, 1993). In this paper, we report our findings on polysomy 12 in 60 consecutive evaluable cases of N H L with FISH.…”

Section: Introductionmentioning

confidence: 89%

Polysomy of chromosome 12 in 60 patients with non‐hodgkin's lymphoma assessed by fluorescence in situ hybridization: Differences between follicular and diffuse large cell lymphoma

Younes

Goodacre

Andreeff

et al. 1994

Genes Chromosomes & Cancer

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Sixty consecutive evaluable specimens from patients with non-Hodgkin's lymphoma (NHL) were studied for the incidence of polysomy of chromosome 12 by fluorescence in situ hybridization (FISH) with probes for the repetitive DNA sequence in the centromeric region of chromosome 12. Thirty-six samples were from follicular lymphomas (FLs), and twenty-four were from diffuse large cell lymphomas (DLCLs). Fifty-two specimens (86%) were obtained by fine-needle aspiration of a diseased node, seven (11.6%) were from involved bone marrows, and one specimen was from a pleural effusion. Twelve of the thirty-six (33%) cases with FL had trisomy 12 in 3-41% of the cells (median, 10%) (normal controls had three signals in 1.4 +/- 0.7% of cells). Trisomy 12 was found in 62% of the patients who had had FL for more than 5 years. Nine of the twenty-four cases (37%) with DLCL had more than two copies of chromosome 12 in 4-92% of the cells (median, 78%), and all nine cases were of B-cell phenotype. Unlike FL cells, some DLCL cells had 4-6 copies of chromosome 12. In previously untreated patients, 54% of DLCLs and 26% of FLs had subpopulations of cells containing more than two copies of chromosome 12 (P = 0.04). Only 2/7 cases of DLCL with polysomy 12 had rearrangement of the BCL2 gene, indicating that the majority of DLCL cases with polysomy 12 did not result from histologic transformation of low grade follicular lymphomas. These data demonstrate that FISH of interphase cells is a sensitive method for detecting numerical abnormalities of chromosome 12 in NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…A mild clinical course was observed in the remaining patient with 6p anomaly, which was apparently not in¯uenced by the presence of 12 in interphase cells. It is worth noting that, whereas 12 in metaphase cells has an unfavourable prognostic signi®cance compared with other single anomalies (Juliusson et al, 1991), the presence of 12 in interphase cells does not per se convey an inferior outcome (Escudier et al, 1993;Bentz et al, 1999). The relatively small size of the trisomic clone in these patients and its low in vitro mitotic index may partially account for this observation.…”

Section: Discussionmentioning

confidence: 99%

Four novel non‐random chromosome rearrangements in B‐cell chronic lymphocytic leukaemia: 6p24–25 and 12p12–13 translocations, 4q21 anomalies and monosomy 21

et al. 2000

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Summary. Nine patients with previously unreported chromosome changes were identi®ed among 209 B-cell chronic lymphocytic leukaemia (CLL) cases: three patients had a translocation involving 6p24±25; three had a 12p12±13 translocation; two had 4q21 involvement (one with coexisting 6p anomaly); and two had monosomy 21.Interphase¯uorescence in situ hybridization (FISH) detected some cryptic aberrations (12, 6q±, 17pÀ, 11qÀ) in those patients with 6p translocations, whereas only a cytogenetically undetected 13q14 deletion was found in the remaining cases.Atypical morphology was noted in six cases, including both cases with monosomy 21, two cases with 6p and 4q21 anomaly and one case with 12p involvement. Four of these cases also had more than one phenotype deviation with respect to the classical CLL phenotype. Disease progression after 21±51 months (median 41) was noted in two cases with 6p and 4q21 involvement and in one case with 12p anomaly and monosomy 21.We arrived at the following conclusions: (i) 6p24±25 and, possibly, 4q21 lesions represent non-random events in CLL, occurring in association with other well-known unbalanced rearrangements; (ii) 12p rearrangements and monosomy 21 may possibly represent early chromosome defects that are not associated with the classical DNA gains and losses known to be present in the majority of CLL; and (iii) atypical morphology and immunophenotype as well as disease progression were frequently observed in these cases

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Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia

Cited by 12 publications

References 0 publications

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Polysomy of chromosome 12 in 60 patients with non‐hodgkin's lymphoma assessed by fluorescence in situ hybridization: Differences between follicular and diffuse large cell lymphoma

Four novel non‐random chromosome rearrangements in B‐cell chronic lymphocytic leukaemia: 6p24–25 and 12p12–13 translocations, 4q21 anomalies and monosomy 21

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