Characterization of a hairy cell leukemia-associated 5q13.3 inversion breakpoint

Wu, Xiushan; Merup, Mats; Juliusson, Gunnar; Jansson, Monika; Stellan, Birgitta; Grandér, Dan; Zabarovsky, Eugene R.; Liu, Yie; Spasokoukotskaja, Tatjana; Gahrton, Gösta; Einhorn, Stefan

doi:10.1002/(sici)1098-2264(199712)20:4<337::aid-gcc4>3.0.co;2-2

Cited by 17 publications

(8 citation statements)

References 30 publications

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“…Although 5q13 abnormalities have not previously been related to SMZL, the region has been involved in hairy cell leukemia. 35,36 The demonstration in the present series of a high incidence of gains on 5q in SMZL, with a consensus region located at 5q13-q15, suggests that this region could be related to SMZL.…”

Section: Discussionmentioning

confidence: 61%

Novel Genomic Imbalances in B-Cell Splenic Marginal Zone Lymphomas Revealed by Comparative Genomic Hybridization and Cytogenetics

Hernández

Garcı́a

Gutiérrez

et al. 2001

The American Journal of Pathology

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Splenic marginal zone lymphoma (SMZL) has recently been recognized in the World Health Organization classification of hematological diseases as distinct type of non-Hodgkin's lymphoma. In contrast to the well-established chromosomal changes associated with other B-cell non-Hodgkin's lymphoma, few genetic alterations have been found associated with SMZL. The aim of our study was to analyze by comparative genomic hybridization (CGH) the chromosomal imbalances in 29 patients with SMZL and to correlate these findings with clinical and biological characteristics and patient outcome. In 21 cases, cytogenetic studies were simultaneously performed. Most of the patients (83%) displayed genomic imbalances. A total of 111 DNA copy number changes were detected with a median of four abnormalities per case (range, 1 to 12). Gains (n ‫؍‬ 92) were more frequent than losses (n ‫؍‬ 16), while three high-level amplifications (3q26-q29, 5p11-p15, and 17q22-q25) were observed. The most frequent gains involved 3q (31%), 5q (28%), 12q and 20q (24% each), 9q (21%), and 4q (17%). Losses were observed in 7q (14%) and 17p (10%). SMZL patients with genetic losses had a shorter survival than the remaining SMZL patients (P < 0.05). Splenic marginal zone lymphoma (SMZL) has been considered a subtype of B-cell non-Hodgkin's lymphoma (NHL) in the recent classification of hematological diseases.1 SMZL has been recognized as a separate entity on the basis of its morphological, phenotypic, and clinical characteristics.2 Several studies have been performed to assess the genetic abnormalities in marginal lymphomas. Recently, two translocations, t(1;14)(p22;q32) involving BCL10/IgH 3 and t(11;18)(q21;q21) -API2/MLT-4 have been described, associated with high-grade and lowgrade MALT lymphomas, respectively. However, genetic information of SMZL is scanty. Cytogenetic analyses have shown involvement of chromosomes 1, 3, 7, and 8. 5,6 Fluorescence in situ hybridization studies on interphase nuclei have demonstrated the presence of trisomy 3 in a proportion of cases ranging from 18 to 47% of SMZL. 6 -9 In previous studies we have reported that in some SMZL cases, the only cytogenetic abnormality displayed was del(7q) that could suggest that del(7q) is associated with SMZL. 6,10 Recently, loss of heterozygosity studies demonstrated that the frequency of allelic loss in SMZL (40%) is higher than that observed in other B-cell lymphoproliferative syndromes. The most frequently deleted microsatellite was D7S487.11 These results are in accordance with our fluorescence in situ hybridization studies that mapped the commonly deleted region in chronic B-cell lymphoproliferative disorders at 7q31.3.

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Section: Discussionmentioning

confidence: 61%

Novel Genomic Imbalances in B-Cell Splenic Marginal Zone Lymphomas Revealed by Comparative Genomic Hybridization and Cytogenetics

Hernández

Garcı́a

Gutiérrez

et al. 2001

The American Journal of Pathology

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“…The same group suggested that 5q13.3 is likely to harbor a gene involved in the transformational event of HCL. 37 Catovsky's group showed clonal chromosome abnormalities in 12 out of 15 HCL patients, of which five had a 14q+. In that study neither chromosome 5, nor 17 were found to be involved.…”

Section: Discussionmentioning

confidence: 99%

P53 mutations in hairy cell leukemia

Kusser

Day

et al. 2000

Leukemia

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We have studied the frequency of p53 mutations in genomic DNA extracted from peripheral blood or the spleen of 61 patients with hairy cell leukemia using PCR-SSCP and automated cycle sequencing. We identified exon 5-8 mutations in 17 cases, corresponding to a frequency of 28%. In four cases, mutations were localized in exon 5; one patient with atypical HCL had a mutation in exon 6 at the 3Ј boundary; five cases showed mutations in exon 7, while exon 8 was found to be mutated in seven cases. The mutations found could be divided into three major categories: structural (n = 9), inactivating (n = 6), and neutral (n = 2) mutations. None of the three transitions found occurred at CpG dinucleotides. The rate of p53 mutations found in this large cohort of HCL patients is unexpectedly high as in other non-Hodgkin lymphomas p53 mutations predict for poor treatment outcome. The character of the mutations we have found is entirely different from that described in other hematologic malignancies. Leukemia (2000) 14, 706-711.

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“…In the case of HCL; however, this strategy has, to date, failed to identify genes or pathways disrupted in more than a small percentage of cases. Previous studies by our group using fluorescent in situ hybridisation (FISH) analysis identified alteration of chromosome 5q13 in a minority of cases (22, 23). Further work revealed disruption of the gene ENC1‐AS in a single case and showed that ENC‐1 is itself highly expressed in HCL, suggesting that ENC‐1 may function in an oncogenic manner in this malignancy.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of hairy cell leukaemia by tiling resolution array‐based comparative Genome hybridisation: a series of 13 cases and review of the literature

Nordgren

Corcoran

Sääf

et al. 2009

European J of Haematology

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Little is known about the cytogenetic features and molecular mechanisms behind hairy cell leukaemia (HCL), despite the advances in diagnosis and treatment. Therefore, we used high-resolution genome-wide array-based comparative genomic hybridisation (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) to characterise copy number alterations (CNAs) in DNA from 13 cases of HCL. We also summarise CNAs and cytogenetic features in 109 HCL cases comprising our 13 cases and 96 cases from the literature. Genomic array-CGH revealed imbalances in two out of 13 cases in addition to previously described copy number variants (CNVs) found in healthy individuals. In one case, a 700 kb deletion of 20q11.22 was detected encompassing ten characterised genes, among them the TP53INP2, DNCL2A and ITCH genes. In the second case, trisomy 5, and a deletion of 5p15.2 encompassing a non-characterised gene AY328033 was found. Altogether only 20/81 (25%) of all cases studied by CGH or gene dose array revealed CNAs. The most common recurrent deletions and breakpoints were 14q22-32 (33%), 6q25 (16%), 2p12 (10%), 22q11 (10%), 17p11-13 (10%), 7q32-36 (9%), 18q11-13 (7%), 1q32-44 (6%), 8p22-23 (6%) and 7q11 (6%). Trisomy 5 occurred in 15%. In addition, several other recurrent breakpoints were identified. Although a number of genomic imbalances were identified in the HCL samples, the genome appeared remarkably stable.

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Characterization of a hairy cell leukemia-associated 5q13.3 inversion breakpoint

Cited by 17 publications

References 30 publications

Novel Genomic Imbalances in B-Cell Splenic Marginal Zone Lymphomas Revealed by Comparative Genomic Hybridization and Cytogenetics

Novel Genomic Imbalances in B-Cell Splenic Marginal Zone Lymphomas Revealed by Comparative Genomic Hybridization and Cytogenetics

P53 mutations in hairy cell leukemia

Characterisation of hairy cell leukaemia by tiling resolution array‐based comparative Genome hybridisation: a series of 13 cases and review of the literature

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