Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and p15CDKN2B genes in certain B cell non-Hodgkin’s lymphomas. Functional studies in a cell line (Granta 519)

Jadayel, D; Lukáš, Jiří; Nacheva, E.; Bártková, Jiřina; Stranks, G; Schouwer, Pierre J. J. C. De; Lens, Daniela; Bártek, Jiří; Dyer, Martin J. S.; Kruger, Anton; Catovsky, Daniel

doi:10.1038/sj.leu.2400555

Cited by 100 publications

(67 citation statements)

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“…Several CKls have been implicated in tumorigenesis in which p16 Ink4a deletion was detected in mouse skin tumors (Linardopoulos et al, 1995) and human tumors (Jadayel et al, 1997;Lilischkis et al, 1996;Musgrove et al, 1995;Schmit et al, 1994). However, the overexpression of p16 Ink4a is consistent with a model in which the loss of pRb function results in the loss of a negative feedback loop.…”

Section: Discussionmentioning

confidence: 99%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16 Ink4a , p57 Kip2 ) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at speci®c times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.

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Section: Discussionmentioning

confidence: 99%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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“…Karpas 422, 26 Ontario Cancer Institute (OCI)-LY1, 27 and NCEB-1 28 were kindly provided by Dr. Neil Berinstein, University of Toronto, Ontario, Canada. Granta 519 29 was obtained from the German Collection of Microorganisms and Cell Cultures (Braunschweig, Germany). Each of these cell lines has a complex karyotype that has previously been published.…”

Section: Cell Linesmentioning

confidence: 99%

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Robetorye

Bohling

Morgan

et al. 2002

The Journal of Molecular Diagnostics

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The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis,The t(14;18) is a frequent chromosomal alteration in nonHodgkin's lymphomas (NHL), occurring in up to 90% of follicular lymphomas 1 and 20 to 30% of diffuse large B-cell lymphomas (DLBCL). 2,3 This translocation is acquired early in B-cell development and results in juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14, resulting deregulated expression of a structurally intact BCL-2 protein. 4 -8 BCL-2 is located in the inner mitochondrial membrane and functions as an anti-apoptotic protein that inhibits programmed cell death, 9 resulting in accumulation of B-lymphocytes by virtue of increased cell survival. 9 -11 Although the t(14;18)-induced over-expression of bcl-2 is an important step in lymphomagenesis, this alteration alone is not sufficient to produce malignant lymphoma. This has been demonstrated in in vitro gene transfer experiments using cell lines and transgenic mice studies in which forced over-expression of bcl-2 was insufficient to cause lymphoma. 12,13 Indeed, low numbers of t(14; 18)-carrying cells can be detected in benign lymphoid tissues such as follicular hyperplasias and the hyperplastic tonsils of young children. 14 These studies indicate that cumulative genetic and cellular alterations superimposed on the t(14;18) are necessary for the development of lymphoma and underscore the need for further analysis of t(14;18)-containing DLBCLs to identify additional genes involved in lymphomagenesis and progression.cDNA microarray technology allows large scale parallel analyses of gene expression and permits simultaneous comparison of the relative gene expression levels of several thousand genes in different cell types. 15,16 This approach has now been used successfully by a number

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“…6,7 These studies predict that tumours with alterations in more than one cell cycle-related gene are likely to have a higher proliferative activity and a more aggressive behaviour than 'one-hit' tumours. MCL are attractive neoplasms to study in this respect because of their consistent overexpression of cyclin D1.…”

Section: Introductionmentioning

confidence: 99%

Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

et al. 1998

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Mantle cell lymphomas (MCL) are morphologically and immunophenotypically distinctive lymphoid neoplasms characterised by overexpression of cyclin D1. Recent studies have suggested that co-operating aberrations of cell cycle associated genes may provide a growth advantage to a tumour. To address this issue further, we investigated five typical and three aggressive (blastoid) MCL for alterations in the cell cycle regulating genes p15, p16, CDK4, Rb and p53. In 3/3 aggressive cases with cyclin D1 overexpression we found aberration of at least one additional gene. One case showed diminished expression of the retinoblastoma protein (pRb); one case harboured deletion of both p15 and p16; and one case exhibited both deletion of p16 and point mutation of p53. However, we also identified two typical cases which in addition to cyclin D1 overexpression exhibited diminished pRb expression and p15 and p16 hypermethylation, respectively. Our findings confirm and extend other recent investigations and indicate that co-operating genetic alterations of cell cycle-associated genes may contribute to the pathogenesis of MCL.

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Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and p15CDKN2B genes in certain B cell non-Hodgkin’s lymphomas. Functional studies in a cell line (Granta 519)

Abstract: Abnormalities of several cell-cycle regulatory genes includingphoma with villous lymphocytes (SLVL) 4 and in some cases type. 14,17,18 We have shown in two cases that biallelic loss of

Cited by 100 publications

References 5 publications

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

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