cyclin-d1 and Epstein-Barr-Virus-Infections

Nasopharyngeal carcinoma (NPC) results from the aberrant and uncontrolled growth of the nasopharyngeal epithelium. It is highly associated with the Epstein-Barr virus, especially in regions where it is endemic. In the last decade, significant advances in genetic sequencing techniques have allowed the discovery of many new abnormal molecular processes that undoubtedly contribute to the establishment, growth and spread of this deadly disease. In this review, we consider NPC as EBV induced. We summarise the recent discoveries and how they add to our understanding of the pathophysiology of NPC in the context of genomics first in primary and then in recurrent disease. Overall, we find key early events lead to p16 inactivation and cyclin D1 expression, allowing latent viral infection. Host and viral factors work together to affect a variety of molecular pathways, the most fundamental being activation of NF-κB. Nonetheless, much still yearns to be discovered, especially in recurrent NPC.

Topics: Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Epstein-Barr Virus Infections; Genomics; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Latent Infection; Nasopharyngeal Carcinoma; Neoplasm Recurrence, Local; NF-kappa B

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that continues to be difficult to treat and cure. In many organ systems and tumor types, there have been significant advances in the understanding of the molecular basis for tumorigenesis, disease progression and genetic implications for therapeutics. Although tumorigenesis pathways and the molecular etiologies of HNSCC have been extensively studied, there are still very few diagnostic clinical applications used in practice today. This review discusses current clinically applicable molecular markers, including viral detection of Epstein-Barr virus and human papillomavirus, and molecular targets that are used in diagnosis and management of HNSCC. The common oncogenes EGFR, RAS, CCND1, BRAF, and PIK3CA and tumor suppressor genes p53, CDKN2A and NOTCH are discussed for their associations with HNSCC. Discussion of markers with potential future applications is also included, with a focus on molecular alterations associated with targeted therapy resistance.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Class I Phosphatidylinositol 3-Kinases; Cyclin D1; Epstein-Barr Virus Infections; Gene Expression Regulation, Neoplastic; Genes, erbB-1; Genes, p16; Genes, p53; Genes, ras; Head and Neck Neoplasms; Humans; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins B-raf; Receptors, Notch; Squamous Cell Carcinoma of Head and Neck

To investigate the clinicopathologic features of mantle cell lymphoma (MCL) involving the oral and maxillofacial region.. The MCL cases were retrieved from the pathosis database of 6 pathology laboratories. Original hematoxylin and eosin slides and immunohistochemical reactions were reviewed for confirmation of the initial diagnosis. Clinical data of the cases were obtained from the patients' pathosis and/or medical charts.. Twenty cases were included in the study, showing a male predominance and a mean age of 66 years. The oral cavity (12 cases) and the oropharynx (5 cases) were the most commonly involved subsites. Most cases presented as asymptomatic swellings, with 2 cases showing bilateral involvement of the palate. The classic histologic variant predominated (12/20 cases). All cases expressed CD20 with nuclear cyclin D1 positivity. SOX11 was seen in 9/13 cases, CD5 in 6/16 cases, Bcl2 in 16/19 cases, CD10 in 2/20 cases, and Bcl6 in 4/16 cases. Ki67 showed a mean proliferation index of 40.6%. The Epstein-Barr virus (EBV) was negative in all cases investigated. Follow-up data was available for 7 patients, with 5 currently alive and 2 deceased.. Mantle cell lymphoma, albeit rare, may manifest in the oral and maxillofacial region. Its histologic heterogeneity demands a high degree of diagnostic skill from pathologists.

Topics: Adult; Aged; Cyclin D1; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Lymphoma, Mantle-Cell; Male

Topics: Cyclin D1; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Receptor Protein-Tyrosine Kinases; Retrospective Studies

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed-Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5

Topics: Aged; Autografts; Biomarkers, Tumor; Cyclin D1; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hodgkin Disease; Humans; In Situ Hybridization, Fluorescence; Lymph Nodes; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Male; Reed-Sternberg Cells; Tumor Suppressor Protein p53

Epstein-Barr virus (EBV), a gamma herpes virus is associated with B-cell malignancies. EBNA-3C is critical for in vitro primary B-cell transformation. Interestingly, the N terminal domain of EBNA3C which contains residues 130-159, interacts with various cellular proteins, such as p53, Mdm2, CyclinD1/Cdk6 complex, and E2F1. In the current reverse genetics study, we deleted the residues 130-159 aa within EBNA3C open reading frame (ORF) by BACmid recombinant engineering methodology. Our experiments demonstrated that deletion of the 130-159 aa showed a reduction in cell proliferation. Also, this recombinant virus showed with higher infectivity of human peripheral blood mononuclear cells (PBMCs) compared to wild type EBV. PBMCs- infected with recombinant EBV deleted for 130-159 residues have differential expression patterns for the p53/Mdm2, CyclinD1/Cdk6 and pRb/E2F1 pathways compared to wild type EBV-infected PBMCs. PBMCs infected with recombinant virus showed increased apoptotic cell death which further resulted in activation of polymerase 1 (PARP1), an important contributor to apoptotic signaling. Interestingly, cells infected with this recombinant virus showed a dramatic decrease in chromosomal instability, indicated by the presence of increased multinucleation and micronucleation. In addition infection with recombinant virus have increased cells in G0/G1 phase and decreased cells in S-G2M phase when compared to wild type infected cells. Thus, these differences in signaling activities due to 29 amino acid residues of EBNA3C is of particular significance in deregulation of cell proliferation in EBV-infected cells.

Topics: Apoptosis; B-Lymphocytes; Cell Line; Cell Proliferation; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cyclin D1; Cyclin-Dependent Kinase 6; E2F1 Transcription Factor; Enzyme Activation; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; HEK293 Cells; Herpesvirus 4, Human; Humans; Leukocytes, Mononuclear; Poly (ADP-Ribose) Polymerase-1; Proto-Oncogene Proteins c-mdm2; Sequence Deletion; Tumor Suppressor Protein p53

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy that exhibits distinct geographical and ethnic prevalence. Although the contemporary therapeutic approach of radio-/chemotherapy provides excellent results for patients with early-stage disease, it is far from satisfactory for those with disease remission and distant metastasis. Promising therapeutic strategies for advanced and relapsed NPC are still lacking. We recently identified and characterized a cancer stem-like cell (CSC) subpopulation in NPC that appeared to play an important role in tumor progression. Microarray analysis revealed downregulation of several stemness-inhibiting miRNAs in these CSC cells. Among these miRNAs, miR-96 and miR-183 showed the highest fold change and were selected to elucidate their role in repressing NPC CSC properties.. MiR-96 and miR-183 expression in NPC CSCs was detected by qRT-PCR. Transient and stable transfection was performed in EBV-positive NPC C666-1 cells to examine the effects of ectopic expression of miR-96 and miR-183 on repressing cell growth and CSC properties. Anchorage-dependent (colony formation) and anchorage-independent (tumor sphere formation) growths of these miR-96 and miR-183 expressing cells were determined. Expression of multiple CSC markers and related molecules were accessed by flow cytometry and Western blotting. The tumorigenicity of the stable miR-96- and miR-183-transfected NPC cells was examined in an in vivo nude mice model.. Downregulation of miR-96 and miR-183 was confirmed in NPC spheroids. Using transient or stable transfection, we showed that ectopic expression of miR-96 and miR-183 suppressed cell growth and tumor sphere formation in NPC. Reduced NICD3 and NICD4 in miR-96- and miR-183-expressing NPC cells suggests the involvement of the NOTCH signaling pathway in their tumor suppressive function. Finally, we showed that the tumorigenicity of cells stably expressing miR-183 was significantly inhibited in the in vivo nude mice model.. miR-183 is a tumor-suppressive miRNA in EBV-associated NPC. Its abilities to suppress CSC properties in vitro and effectively reduce tumor growth in vivo shed light on its role as a potential therapeutic target.

Topics: Animals; Blotting, Western; Cell Line, Tumor; Cyclin D1; Epstein-Barr Virus Infections; Female; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Nasopharyngeal Neoplasms; Neoplastic Stem Cells; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins; Receptor, Notch3; Receptor, Notch4; Receptors, Notch; Reverse Transcriptase Polymerase Chain Reaction; Spheroids, Cellular; Transplantation, Heterologous

Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.

Topics: Base Sequence; Cell Cycle; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellular Senescence; Cyclin D1; DNA, Viral; Epithelial Cells; Epstein-Barr Virus Infections; Gene Expression; Genes, bcl-1; Genes, Viral; Herpesvirus 4, Human; Humans; Nasopharyngeal Neoplasms; Nasopharynx; Precancerous Conditions; Signal Transduction; Telomerase

EBNA3C, one of the Epstein-Barr virus (EBV)-encoded latent antigens, is essential for primary B-cell transformation. Cyclin D1, a key regulator of G1 to S phase progression, is tightly associated and aberrantly expressed in numerous human cancers. Previously, EBNA3C was shown to bind to Cyclin D1 in vitro along with Cyclin A and Cyclin E. In the present study, we provide evidence which demonstrates that EBNA3C forms a complex with Cyclin D1 in human cells. Detailed mapping experiments show that a small N-terminal region which lies between amino acids 130-160 of EBNA3C binds to two different sites of Cyclin D1- the N-terminal pRb binding domain (residues 1-50), and C-terminal domain (residues 171-240), known to regulate Cyclin D1 stability. Cyclin D1 is short-lived and ubiquitin-mediated proteasomal degradation has been targeted as a means of therapeutic intervention. Here, we show that EBNA3C stabilizes Cyclin D1 through inhibition of its poly-ubiquitination, and also increases its nuclear localization by blocking GSK3β activity. We further show that EBNA3C enhances the kinase activity of Cyclin D1/CDK6 which enables subsequent ubiquitination and degradation of pRb. EBNA3C together with Cyclin D1-CDK6 complex also efficiently nullifies the inhibitory effect of pRb on cell growth. Moreover, an sh-RNA based strategy for knock-down of both cyclin D1 and EBNA3C genes in EBV transformed lymphoblastoid cell lines (LCLs) shows a significant reduction in cell-growth. Based on these results, we propose that EBNA3C can stabilize as well as enhance the functional activity of Cyclin D1 thereby facilitating the G1-S transition in EBV transformed lymphoblastoid cell lines.

Topics: Antigens, Viral; Cell Transformation, Viral; Cells, Cultured; Cyclin D1; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; G1 Phase; Gene Expression Regulation; Herpesvirus 4, Human; Humans; Protein Binding; Protein Processing, Post-Translational; Protein Stability; Protein Structure, Tertiary; S Phase; Ubiquitination; Up-Regulation

We present common cytogenetic features in the largest cohort of plasmablastic lymphoma (PBL) of the oral cavity published to date. This cohort included 45 patients, 32 of whom had a known HIV status, of which 31 were HIV positive. Ninety eight per cent of all PBL cases were known to be EBV positive. In line with previous studies, we found that rearrangements of the MYC gene was the most common genetic abnormality seen in 60% of cases with the immunoglobulin heavy chain (IGH) locus as a partner in 51% of cases. Additional complex genetic aberrations were frequent, in particular, an increased copy number of the CCND1 gene was seen in 41% of cases with true amplification of CCND1 in 15% of cases. Aneuploidy was also observed for the BCL6 gene in 28% of cases. Interestingly, rearrangements of both IGH genes were detected in 16% of cases with t(14;18) and t(11;14) respectively involved in conjunction with a t(8;14) in two cases. These bi-allelic IGH rearrangements have not been described before in oral PBL. Our results reinforce the notion that EBV infection and MYC rearrangements are important events in the pathogenesis of oral PBL. The genetic diversity and complexity observed in these cases, underlines the importance to genetically characterise PBL patients at presentation as this may inform the choice of more effective treatment modalities.

Topics: Adult; Aneuploidy; Cohort Studies; Cyclin D1; DNA-Binding Proteins; Epstein-Barr Virus Infections; Female; Gene Rearrangement; Genes, myc; Humans; Immunoglobulin Heavy Chains; In Situ Hybridization, Fluorescence; Lymphoma, AIDS-Related; Male; Middle Aged; Mouth Neoplasms; Proto-Oncogene Proteins c-bcl-6

To investigate the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in Guangzhou, their clinicopathologic features and related protein expressions including DNMT1, p16, and cyclin D1.. A total of 676 cases of EBV-associated gastric carcinoma were included in the study. The presence of EBV-encoded small RNA1 (EBER1), a marker for EBV infection, was analyzed by in-situ hybridization using formalin-fixed and paraffin-embedded tumor samples. Expression of EBV-encoded proteins, DNMT1, p16 and cyclin D1 were detected by immunohistochemistry.. Forty-five of 676 gastric carcinomas showed EBER intranuclear positivity in all tumor cells. EBV involvement was significantly more frequent among the male than the female patients, especially in tumors of less differentiated types (diffuse type) and involving the upper stomach (P < 0.05). EBNA1 and LMP2A expression were detected in 42 (93.3%) and 24 (53.3%) cases, respectively. None expressed EBNA2, LMP1, and ZEBRA. Among 45 cases of EBV associated gastric carcinomas, DNMT1, p16 and cyclin D1 expression were seen in 35 (77.8%), 10 (22.2%), and 29 (64.4%) cases, respectively. In contrast, among 40 EBV negative gastric carcinomas, expression of the three proteins were 20 (50.0%), 25 (62.5%) and 12 (30.0%), respectively. The difference of expression of the three proteins between the two groups was significant (P < 0.05). Expression of p16 correlated with the depth of the tumor invasion. Correlated protein expression was seen between LMP2A and DNMT1, between DNMT1 and p16, and between p16 and cyclin D1 (P < 0.05).. EBV associated gastric carcinoma accounts for 6.7% of gastric carcinomas in Guangzhou with the Latency I pattern in some cases and between Latency I and II in others. The correlated expression of LMP2A, DNMT1, p16 and cyclin D1 may contribute to the pathogenesis of EBV associated gastric carcinomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; China; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Herpesvirus 4, Human; Humans; Male; Middle Aged; Neoplasm Invasiveness; RNA, Viral; Sex Factors; Stomach Neoplasms; Viral Matrix Proteins; Young Adult

Previous studies have revealed that Epstein-Barr virus (EBV) was closely associated with nasopharyngeal carcinoma (NPC). This study aimed to characterize the global pathways affected in the EBV-associated NPC. Combined with microdissection, gene expression profiles in 22 NPCs and 10 non-tumor nasopharyngeal epithelial (NPE) tissue samples were analyzed. All NPC specimens served in the microarray analysis were positive for EBV, as judged by identification of the expression of EBV nuclear antigen 1 (EBNA1). Through gene set enrichment analysis (GSEA), we found that cell cycle pathway was the most disregulated pathway in NPC (P=0.000, false discovery rate q-value=0.007), which included some aberrant expressed components. We first found that overexpression of CDK4, cyclin D1, and Rb proteins, and loss of expression of proteins p16, p27, and p19 were statistically significant in NPC tissues compared with non-cancerous NPE (P<0.05) by real-time RT-PCR and tissue microarray. EBV-encoded small RNA-1 (EBER-1) hybridization signals in the NPC showed significant associations with the overexpression of Rb (P=0.000), cyclin D1 (P=0.000), CDK4 (P=0.000), and the loss of expression of p16 proteins (P=0.039). In the final logistic regression analysis model, EBER-1 and abnormal expression of p16, Rb, cyclin D1, and E2F6 were independent contributions to nasopharyngeal carcinogenesis. Through survival analysis, only cyclin D1 could predict the prognosis of NPC patients. These results suggested that cell cycle pathway was the most disregulated pathway in the EBV-associated NPC, and EBER-1 was closely associated with p16, CDK4, cyclin D1, and Rb.cyclin D1 could be the prognosis biomarker for NPC.

Topics: Cell Cycle; Cell Cycle Proteins; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p19; Cyclin-Dependent Kinase Inhibitor p27; E2F6 Transcription Factor; Epstein-Barr Virus Infections; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Immunohistochemistry; In Situ Hybridization; Kaplan-Meier Estimate; Logistic Models; Nasopharyngeal Neoplasms; Oligonucleotide Array Sequence Analysis; Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Tissue Array Analysis

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV-encoded proteins and has always been the core of the oncogenic mechanism of EBV. Advanced studies on nuclear translocation of the epidermal growth factor receptor (EGFR) family have greatly improved our knowledge of the biological function of cell surface receptors. In this study, we used the Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1-integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 which could be regulated by the Tet system. We found that LMP1 could regulate the nuclear accumulation of EGFR in a dose-dependent manner quantitatively and qualitatively. We also demonstrated that the nuclear localization sequence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation and EGFR in the nucleus could bind to the promoters of cyclinD1 and cyclinE, respectively. We further demonstrated that EGFR is involved in the acceleration of the G1/S phase transition by LMP1 through binding to cyclinD1 and cyclinE directly. These findings provided a novel view that the acceleration of LMP1 on the G1/S transition via the nuclear accumulation of EGFR was critical in the process of nasopharyngeal carcinoma.

Topics: Base Sequence; Cell Line, Tumor; Cell Nucleus; Cyclin D1; Cyclin E; DNA, Neoplasm; Epstein-Barr Virus Infections; ErbB Receptors; G1 Phase; Herpesvirus 4, Human; Humans; Nasopharyngeal Neoplasms; Promoter Regions, Genetic; Protein Binding; S Phase; Viral Matrix Proteins

The mechanism by which Epstein-Barr virus (EBV) contributes to the carcinogenesis of gastric mucosa remains unanswered. In this study, the role of cell-cycle regulators (p53, p21, p27, p16, cyclin D1, Rb), bcl-2 and NF-kappaB p65 (Rel A) was evaluated. Immunohistochemistry for these proteins was performed in EBV-positive (n=55) and EBV-negative gastric carcinomas (n=72). The bcl-2 protein by western blot and EBV transcripts using RT-PCR were studied in cell lines. The p27 loss, p16 loss, cyclin D1 expression and NF-kappaB nuclear positivity were more frequent in EBV-positive gastric carcinomas than those in EBV-negative gastric carcinomas, while p53 overexpression seldom occurred in EBV-positive carcinomas (p<0.001). EBV-positive gastric carcinoma showed unique p53 immunostaining (heterogeneous, weak to moderate, focal staining), and rare bcl-2 positivity (1 case). Western blot showed bcl-2 to be irrespective of EBV status in stomach cancer cell lines. However, bcl-2 was highly expressed in EBV-positive lymphoma or EBV-positive lymphoblastoid cell lines. The BARF1 transcript was confirmed in both EBV-positive stomach cancer and EBV-positive lymphoma, suggesting tissue type-specific bcl-2 activation by BARF1. The pathological tumor stage was the only independent prognostic factor. A small size of tumor, p16 preservation and NF-kappaB nuclear positivity were associated with a good prognosis in univariate analysis (p<0.05). p27, p16, cyclin D1 and NF-kappaB may be associated with oncogenesis in EBV-positive gastric carcinomas. EBV-positive gastric carcinomas showed infrequent p53 overexpression, wild-type p53 stabilization and rare bcl-2 involvement. The characteristic expression of proteins may relate to both EBV and tissue type.

Topics: Adolescent; Adult; Aged; Blotting, Western; Carcinoma; Cell Cycle; Cell Transformation, Neoplastic; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Epstein-Barr Virus Infections; Female; Gene Expression Profiling; Herpesvirus 4, Human; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; NF-kappa B; Prognosis; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Up-Regulation

The t(11;14)(q13;q32) translocation with cyclin D1 overexpression commonly is found in multiple myeloma (MM) and in mantle cell lymphoma (MCL). Several reports have shown that p53 mutations in MCL lead to blastoid transformation and a worse prognosis; however, the role of p53 mutations in MM with t(11;14) is unclear.. In this study the authors describe a patient with MM with t(11;14) and a p53 mutation at presentation and characterized a cell line, MEF-1, established from this patient. Immunohistochemical analysis of p53 and cyclin D1 proteins was performed. The p53 gene was analyzed by polymerase chain reaction-single strand conformation polymorphism and direct sequencing. The expression of cyclin D1 mRNA was examined by Northern blot analysis.. MEF-1 had t(11;14) with overexpression of cyclin D1 mRNA and produced immunoglobulin kappa-light chain. MEF-1 had a mutation in exon 7 (codon 255-257) of the p53 gene, which was noted in the patient's myeloma cells.. p53 mutations may be important genetic events in disease progression of MM with t(11;14). The MEF-1 cell line may be a useful tool to study mechanisms of progression in MM based on abnormalities of the cyclin D1 gene.

Topics: Aged; Bone Marrow; Bone Neoplasms; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Epstein-Barr Virus Infections; Fatal Outcome; Female; Forearm; Gene Expression Regulation, Neoplastic; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes, p53; Herpesvirus 4, Human; Humans; Immunophenotyping; Karyotyping; Multiple Myeloma; Myeloma Proteins; Neoplasm Proteins; Polymorphism, Single-Stranded Conformational; Translocation, Genetic; Tumor Cells, Cultured