BCL-2 oncoprotein in neuroblastoma

Weinreb, Miron; Day, Pjr; Niggli, Felix; Raafat, F.; Mann, J R

doi:10.1016/s0140-6736(95)90743-2

Cited by 5 publications

(3 citation statements)

References 2 publications

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“…The EBV type 2 has been detected in 50% of endemic BL [20,21] whereas it is found in 10-20% of EBV-associated BL in sporadic regions such as United State of America, Egypt, and Brazil. Similarly 50% of HL in Africa contains EBV type 2 [22], while the percentage of HL with type 2 in America and Europe is low [1]. These evidences point to an uneven geographical distribution of EBV types, while the role of EBV gene variation in pathogenesis is less clear so far.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1

et al. 2008

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Genetic variation in tumor virus genes and its impact on function might contribute to the understanding of geographic differences in risks for virus-associated tumors. This is particularly true for the genes known to contribute to the biology of the tumor. It is has been proposed that Epstein-Barr virus (EBV) gene variation has a role in the high risk of nasopharyngeal carcinoma (NPC) in South-East Asia. NPC is among the five most common cancers in Vietnam. EBV-NPC cells always express EBV nuclear antigen 1 (EBNA1) and also frequently latent membrane protein 1 and 2 (LMP1 & LMP2). To investigate EBV gene variation in Vietnamese NPC patients we analyzed the full length of LMP1 gene including its promoter region, and the N-termini of both EBNA1 and LMP2A genes from five NPC biopsies. We detected two EBV variants V1 and V2 based on the LMP1 nucleotide sequence pattern compared with the prototype B95-8 and some available sequences including Chinese variants. The V1 variant shows strong similarity to a variant dominant in Southern China (China 1), while the V2 variant is similar to a Thai variant SEA 2 and partly identity with GD1 in the C-terminus. The promoter region and transmembrane domain of the SEA 2-like samples contained some specific differences compared with previously published variants. In contrast, analysis of EBNA1 N- and LMP2A N-termini only revealed minor changes. Our findings reinforces that the polymorphisms of whole LMP1 sequence should be considered in future EBV molecular epidemiology studies in different geographic populations.

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Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1

et al. 2008

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“…Studies have often shown small cohorts, concentrated on rare forms of NB, or lacked sufficient clinical data about the course of disease. 22,39 More detailed approaches focus on artificial, controllable conditions as in cell lines or in vivo experiments with mice, but hardly in native human tumor tissue. 40 It has to be mentioned that previous studies revealed a gross difference of BCL-2 gene expression between human NB tissue and cell lines.…”

Section: Discussionmentioning

confidence: 99%

Impact of BCL-2 Expression on Course of Disease in Neuroblastoma

Muehling,

Fröba-Pohl,

Muensterer

et al. 2023

Eur J Pediatr Surg

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Objective The antiapoptotic BCL-2 protein has implications for maturation and differentiation of neural tissue and acts as a strong modulator of carcinogenesis in different tumors. Recent research focuses not only on its benefit as a prognostic factor, but also as a potential therapeutic target. The role of BCL-2 in neuroblastoma, the most common extracranial solid tumor in childhood, remains controversial. The aim of our study was to determine the gene expression level of BCL-2 in a large cohort of neuroblastoma patients and its correlation with clinical parameters. Methods Tumor samples and clinical data were collected from 100 neuroblastoma patients treated according to the NB2004 protocol of the German Society of Pediatric Oncology and Hematology. BCL-2 gene expression levels were measured by quantitative reverse transcription polymerase chain reaction and correlated with clinical parameters. Results BCL-2 expression was detected in all tumor samples. Relative BCL-2 expression levels were higher in females versus males (1.839 vs. 1.342; p = 0.0143), in patients with low versus high International Neuroblastoma Staging System stage (2.051 vs. 1.463; p = 0.0206), in nonmetastatic versus metastatic disease (1.801 vs. 1.342; p = 0.0242), as well as in patients without presurgical chemotherapy (2.145 vs. 1.402; p = 0.0016), but was not associated with overall survival and MYCN amplification. Conclusion Our study demonstrates the ubiquitous expression of BCL-2 in neuroblastoma and suggests the possibility for targeted therapy with BCL-2 inhibitors, even in lower-stage neuroblastoma. It also underlines the need for further research on concomitant genetic alterations for a better understanding of the impact of BCL-2 on this pediatric tumor type.

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“…Castle et al 11 have shown that BCL-2 protein is associated with unfavorable histology and that it is detectable in undifferentiated neuroblastoma cells. Conversely, Weinreh et al 12 reported that BCL-2 protein was ubiquitously expressed in all neuroblastoma tissues they examined without correlation between BCL-2 and unfavorable stages. Furthermore, Lasorella et al 13 reported that BCL-2 expression was associated with the induction of drug resistance in neuroblastoma cells.…”

Section: Introductionmentioning

confidence: 94%

Apoptosis and expression of bcl-2 ?, ? mRNA isoforms and protein in neuroblastoma

Mazzocco¹,

Scaruffi²,

Gambini

et al. 1996

Apoptosis

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We studied apoptosis in 36 neuroblastomas by DNA ladder assay. Expression of bcl2-cx and [3 mRNA isoforms and protein were detected by RT-PCR and by immunohistochemistry, respectively. Internucleosomal DNA fragmentation was found in 20/36 (56%) tumor tissues collected both at onset and relapse of disease. Bcl-2c~ and 13 mRNAs and protein were found in almost all examined tumors irrespective of DNA ladder, thus showing lack of correlation with the clinical stage. BCL-2 protein was observed to be expressed at various levels in undifferentiated and in more differentiated neuroblasts, while the stroma and the fibrovascular tissue were negative. Our results show that apoptosis is present in neuroblastoma at all stages and that bcl-2 gene is widely expressed in tumor tissue. In our series of neuroblastomas, bcl-2 expression is not correlated with unfavorable prognosis.

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BCL-2 oncoprotein in neuroblastoma

Cited by 5 publications

References 2 publications

Epstein-Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1

Epstein-Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1

Impact of BCL-2 Expression on Course of Disease in Neuroblastoma

Apoptosis and expression of bcl-2 ?, ? mRNA isoforms and protein in neuroblastoma

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