Chromosome Aberrations in Adult Hodgkin Disease in a Danish Population-Based Study

Pedersen, Rikke K.; Sørensen, Anne G.; Pedersen, Niels Tinggaard; Schmidt, Kjeld; Kerndrup, Gitte

doi:10.1016/s0165-4608(98)00204-0

Cited by 12 publications

(4 citation statements)

References 21 publications

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“…[2,3] By applying array-based comparative genomic hybridization (CGH) to microdissected HRS cells, recurrent gains and recurrent losses involving 35 putative cancer genes were detected. [4,5] More recently, gene expression profiling of microdissected HRS cells identified 21 genes whose expression differed significantly from that of non-Hodgkin B cell lymphoma. [6] A few HRS cell lines have been established from cases of classical Hodgkin lymphoma (HL).…”

Section: Introductionmentioning

confidence: 99%

Recurrent genetic defects in classical Hodgkin lymphoma cell lines

Hudnall

Meng

Lozovatsky

et al. 2016

Leukemia & Lymphoma

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Genetic analysis of classical Hodgkin lymphoma (cHL) has been hampered by the paucity of Hodgkin cells in biopsies and their poor growth in vitro. However, a wealth of information has been obtained from cHL cell lines. Here we report results of whole-exome sequencing and karyotypic analysis of five cHL cell lines. Four genes with potentially pathogenic single nucleotide variants (SNV) were detected in three cell lines. SNV were also detected in seventeen HL-related genes and three mitosis-related genes. Copy number variants were detected in four HL-related genes in all five cell lines. Given the high degree of aneuploidy in HL, mitosis-related genes were screened for defects. One mitotic gene (NCAPD2) was amplified in all five HL cell lines, and two genes (FAM190A, PLK4) were amplified in four cell lines. These results suggest that genomic instability of HL may be due to defects in genes involved in chromosome duplication and segregation.

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Section: Introductionmentioning

confidence: 99%

Recurrent genetic defects in classical Hodgkin lymphoma cell lines

Hudnall

Meng

Lozovatsky

et al. 2016

Leukemia & Lymphoma

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“…on August 29, 2018. by guest www.bloodjournal.org From a number of nonrandom changes associated with HL, additional copies of chromosomes 2, 5, 9, and 12 were observed by several groups in up to 46% of cases. [30][31][32][33][34][35] However, a wide range of other chromosomes was found to be affected by numerical changes, and the significance of individual aberrations was thus difficult to estimate. By measuring net chromosomal gains and losses in pools of HRS cells, a more specific pattern of recurrent chromosomal imbalances was detected that involved relatively few chromosomal arms or subregions (eg, 2p15-p16, 9p23-p24, 12q24, 13q14-q21, 16p and 17).…”

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Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2

Joos

Menz

Wrobel

et al. 2002

Blood

215

138

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IntroductionHodgkin lymphoma (HL), which accounts for approximately one third of all malignant lymphomas, is characterized by the presence of only a small fraction of malignant cells. Neoplastic cells represented as mononucleated Hodgkin-and multinucleated Reed-Sternberg cells (HRS cells) are embedded in a varying infiltrate of reactive cells including B and T lymphocytes, eosinophils, plasma cells, and fibroblasts. 1 According to the new World Health Organization (WHO) classification, 2 4 well-defined histotypes of classical Hodgkin lymphoma (cHL) can be distinguished: lymphocyte-rich (cHL-LR), nodularsclerosis (cHL-NS), mixed-cellularity (cHL-MC), and lymphocytedepletion (cHL-LD). Paragranuloma (nodular lymphocyte predominant Hodgkin lymphoma [NLPHL]) has been shown to be clinically and immunophenotypically distinct and eventually to transform to large B-cell non-Hodgkin lymphoma. This indicates that NLPHL is essentially different from the cHL subtypes.Because of the small number of malignant cells, cytogenetic analysis is particularly difficult in HL and, to date, has not revealed any specific chromosomal rearrangements. Detailed analysis by chromosome banding is further limited by the low mitotic index of neoplastic cells, frequently poor chromosome morphology, and complex karyotypic rearrangements. For these reasons, it is difficult to obtain sufficient numbers of karyotypes for evaluation that are representative of the malignant cell population. 3,4 Alternatively, combined immunohistochemical and cytogenetic analyses by fluorescence in situ hybridization (FISH) have been applied. It could be demonstrated that chromosomal changes are almost exclusively restricted to CD30 ϩ HRS cells. Furthermore, significant heterogeneity in terms of the copy number of single chromosomes was detected using this approach. [5][6][7][8] Recently, comparative genomic hybridization (CGH) was applied in combination with universal polymerase chain reaction (PCR) technology for cytogenetic analyses of HRS cells. 9-11 These analyses indicated higher rates of numerical aberrations of individual chromosomes than had previously been found by banding analysis, in which the identification of numerical changes is difficult because of the complex karyotypes of HRS cells. Gains and losses in more than 50% of the cHL tumors were identified on chromosomal arms 2p, 7q, and 16q, 9,10 whereas in NLPHL, chromosomal arms 1q, 3p, 5q, and Xq were affected. 11 Although the number of analyses is still low (20 cHLs and 20 NLPHLs to date), CGH has already allowed the identification of several imbalanced chromosomal subregions, indicating the localization of candidate genes that may be involved in the etiology of this disease.To further define critical subregions in cHL, a series of 41 tumors was analyzed (a small subset of cases was reported recently 10 ). To this end, collected pools of approximately 30 malignant HRS cells from single tumors were isolated using microdissection technology. Genomic DNA from the individual cell pools was subsequently ampl...

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“…To the best of our knowledge, only 9 LPHD cases with clonal chromosomal abnormalities have been reported. 17,18,[26][27][28][29][30][31] Five of these revealed hyperdiploid karyotypes and most showed complex chromosomal aberrations.In this study, we investigated a series of 19 LPHD cases by using CGH. Because of the low number of neoplastic cells in LPHD, the analysis was performed on degenerate oligonucleotide primed-PCR (DOP-PCR)-amplified DNA obtained from microdissected CD20 ϩ "popcorn" cells.…”

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Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances

Franke

Włodarska

Maes

et al. 2001

Blood

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IntroductionHodgkin disease (HD), one of the most common malignant lymphomas in the western world, was first described by Thomas Hodgkin in 1832. The characteristic morphologic feature of HD is the cellular composition of the tumor tissue containing a small number (approximately 0.1% to 1%) of neoplastic ReedSternberg (RS) cells and a major population of nonneoplastic lymphocytes, histiocytes, neutrophils, fibroblasts, eosinophils, and plasma cells. On the basis of tumor cell morphology, immunophenotype, and the composition of the cellular background, 2 separate biologic entities, namely, lymphocyte predominance Hodgkin disease (LPHD) (or nodular paragranuloma) and classical HD have been recognized in the Revised European-American Lymphoma (REAL) classification. 1 LPHD accounts for 5% of all HD cases. Typically, patients are 25-to 45-year-old men and usually present at an early clinical stage. More than 90% of patients with LPHD have a complete response to therapy, although recurrences frequently occur. In LPHD, a particular variant of RS cells, the "popcorn" or lymphocytic and histiocytic (L&H) cells, is found. In contrast to RS cells of classical HD, "popcorn" cells lack the expression of CD30 and CD15 but express CD45 and CD20. The expression of these markers and presence of nodular structures closely resembling lymphoid B follicles have suggested that "popcorn" cells represent neoplastic germinal center B cells. [2][3][4] Because of the very low frequency of RS and "popcorn" cells in the tumor tissue and the lack of suitable methods for their purification and analysis, clonality and lineage derivation of neoplastic cells in HD have remained uncertain until recently. As soon as single-cell polymerase chain reaction (PCR)-based methods had been developed, clonal Ig rearrangement and consistent occurrence of somatic mutations within the variableregions of Ig genes amplified from isolated RS and "popcorn" cells have been demonstrated in the majority of analyzed cases. These findings indicated a clonal germinal-center (GC) or post-GC B-cell origin of LPHD as well as of classical HD. [5][6][7][8][9][10][11] On the other hand, polyclonal Ig rearrangements found in some HD cases 12-14 led to the hypothesis of a sequential poly-/oligo-/monoclonal origin of HD, a matter that is still under discussion. [15][16] Despite recent progress in HD research, genetic and molecular data are only scarcely available. There are intrinsic technical problems in obtaining metaphase chromosomes in HD (low number of RS cells, low proliferation index, infiltration of reactive cells), and therefore no more than 200 HD cases with [19][20][21] and by comparative genomic hybridization (CGH), 22,23 so far no specific cytogenetic marker(s) could be identified. Single RScell PCR analysis of CMYC, BCL2, and BCL1 suggested that these non-Hodgkin lymphoma (NHL)-specific genes are not involved in the pathogenesis of HD. 24,25 Even less is known about genetic and molecular aberrations in the LP subtype of HD. To the best of our knowledge, only 9 LP...

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Chromosome Aberrations in Adult Hodgkin Disease in a Danish Population-Based Study

Cited by 12 publications

References 21 publications

Recurrent genetic defects in classical Hodgkin lymphoma cell lines

Recurrent genetic defects in classical Hodgkin lymphoma cell lines

Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2

Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances

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