Epstein-Barr virus and cancers of the head and neck

Goldenberg, David; Golz, Avishay; Netzer, Aviram; Rosenblatt, E.; Rachmiel, Adi; Goldenberg, Renee Flax; Joachims, Henry Z.

doi:10.1053/ajot.2001.23429

Cited by 39 publications

(29 citation statements)

References 48 publications

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“…Nasopharyngeal carcinoma is 100% EBV positive (43), and gastric carcinomas are 10% positive worldwide, with up to 18% positivity in some regions (48). A number of rarer carcinomas, such as lymphoepithelioma-like carcinomas of the salivary gland, lung, and thymus, are also EBV associated (21). The presence of EBV DNA in breast cancer was first reported in 1995 by Labrecque et al (30).…”

Section: Discussionmentioning

confidence: 99%

Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Huang¹,

Chen

Hutt-Fletcher

et al. 2003

J Virol

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Epstein-Barr virus (EBV)has an accepted association with the epithelial malignancy nasopharyngeal carcinoma and has also been reported in other more controversial carcinoma settings. Evaluation of EBV association with epithelial carcinomas such as breast cancer would benefit from a better understanding of the outcome of EBV infection of these cells. Cell-free preparations of a green fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell lines, which were then examined for EBV gene expression and viral genome copy number. Reverse transcription-PCR analyses revealed that the cells supported a mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein expression was detected by immunohistochemistry, and DNA PCR analyses estimated an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic EBV expression was also found in breast tissue, where reverse transcription-PCR analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4 of 10 normal tissues from the same patients. Scattered cells immunoreactive for Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1% of the cells contained viral genomes. We suggest that sporadic lytic EBV infection may contribute to PCR-based detection of EBV in traditionally nonvirally associated epithelial malignancies.

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Section: Discussionmentioning

confidence: 99%

Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Huang¹,

Chen

Hutt-Fletcher

et al. 2003

J Virol

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“…Nasopharyngeal carcinoma (NPC), with a unique geographical and ethnic distribution and high radio-and chemosensitivity, is usually considered separately from other head and neck carcinomas. The undifferentiated subtype of NPC has a strong association with EBV (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…It is present in the tumor tissue of nasopharyngeal undifferentiated carcinoma and various lymphoid malignancies (1)(2)(3)(4)(5). The virus is also present in the tumor cells of a number of NNHNC (6 -15).…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Analysis of Cell-Free Epstein-Barr Virus DNA in Plasma of Patients with Nonnasopharyngeal Head and Neck Carcinomas

Yu¹,

Tse

et al. 2004

Clinical Cancer Research

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Purpose: We investigated the detectability of EBV DNA in the plasma of patients with non-nasopharyngeal head and neck carcinomas (NNHNC). Previous studies have shown that EBV is present in the tumor tissue of some NNHNC.Experimental Design: We recruited 101 patients with NNHNC and 48 healthy controls. Blood samples were taken from controls and patients before treatment. Tumor tissue samples were tested for the presence of EBV in the first 69 patients by in situ hybridization for small EBV-encoded RNA (EBER). Plasma EBV DNA was measured by real-time quantitative PCR in patients and controls.Results: Squamous cell carcinoma (SCC) was the commonest histology (78 patients) followed by lymphoepithelial carcinoma (8 patients). EBER was detected in tumor cells in 7 of 69 patients tested. All of the EBER-positive tumors were lymphoepithelial carcinoma. Two controls (2 of 48; 4.2%) had detectable plasma EBV DNA. Plasma EBV DNA was detected in all of the patients with EBER-positive tumors, and in 23 of 94 (24.5%) patients with tumors of EBERnegative or unknown status. The proportion of plasma EBV DNA-positive cases in either group was significantly higher than that in the control group (P < 0.0027). Plasma EBV DNA concentrations in patients with EBER-positive tumors (median, 3827 copies/ml) were significantly higher than those in the controls (median, 0 copy/ml; P ‫؍‬ 0.0001). Of patients with SCC, 21 (26.9%) had detectable plasma EBV DNA (median concentration, 34 copies/ml). Plasma EBV DNA concentrations in the whole group of patients with SCC (median, 0 copy/ml; interquartile range, 0 -4 copies/ ml) were also significantly higher than those in the controls (P ‫؍‬ 0.001).Conclusions: Our data indicate that plasma EBV DNA reflects tumoral EBER status, and it may be of use as a tumor marker for EBER-positive NNHNC. The biological and clinical significance of low levels of circulating EBV DNA in the minority of patients with EBER-negative tumors remain to be elucidated.

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“…LSCC occurrence is associated with tobacco smoking and alcohol intake (1) as well as viral infections by HPV (2) or EBV (3). A substantial disproportion between smoking and drinking male and female individuals (8-10:1) diagnosed with LSCC is observed.…”

Section: Introductionmentioning

confidence: 99%

Pyrosequencing-based DNA methylation profiling of Fanconi anemia/BRCA pathway genes in laryngeal squamous cell carcinoma

Szaumkessel¹

2011

Int J Oncol

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Abstract. Fanconi anemia (FA) associated genes [FANCA, -B, -C, FANCD1(BRCA2), -D2, -E, -F, -G, -I, -L, -M, FANCN (PALB2), FANCJ(BRIP1)and FA-linked BRCA1] encode proteins of DNA damage response pathways mutated in FA patients. FA is characterized by congenital malformations, chromosomal instability and high cancer susceptibility. FA patients have a 500-700 times higher risk of head and neck squamous cell carcinoma (HNSCC) compared to the non-FA population. As DNA methylation comprises one of the known gene inactivation mechanisms in cancer we have investigated the methylation status of 13 FA and one FA-linked gene in order to assess the role of FA in sporadic laryngeal squamous cell carcinoma (LSCC) tumor samples. Thirteen laryngeal squamous carcinoma cell lines (UT-SCC) and 64 primary laryngeal carcinoma cases were analyzed by bisulfite pyrosequencing. DNA from buccal swabs of 10 healthy volunteers was used as a control group. Promoter regions of FANCA, BRCA1 and BRCA2 displayed recurrent alterations in the methylation levels in cancer samples as compared to buccal swabs controls. For FANCA, hypomethylation was observed in 11/13 cell lines (p<0.0003) and all 64 primary larynx samples (p<0.001) compared to buccal swabs. For BRCA1, 4/13 cell lines (p=0.04) and 3/58 primary laryngeal cases (p=0.22) showed hypomethylation. In BRCA2, all 13 cell lines (p<0.0001) 4/63 primary LSCC (p<0.01) showed hypermethylation as compared to controls. In conclusion, we show recurrent alterations of DNA methylation levels in three Fanconi anemia genes which might contribute to the pathogenesis of LSCC.

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Epstein-Barr virus and cancers of the head and neck

Cited by 39 publications

References 48 publications

Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Quantitative Analysis of Cell-Free Epstein-Barr Virus DNA in Plasma of Patients with Nonnasopharyngeal Head and Neck Carcinomas

Pyrosequencing-based DNA methylation profiling of Fanconi anemia/BRCA pathway genes in laryngeal squamous cell carcinoma

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