Conserved Methylation Patterns of Human Papillomavirus Type 16 DNA in Asymptomatic Infection and Cervical Neoplasia

Kalantari, Mina; Calleja-Macías, Itzel E.; Tewari, Devansu; Hagmar, Björn; Lie, Kathrine A.; Barrera-Saldaña, Hugo A.; Wiley, Dorothy J.; Bernard, Hans‐Ulrich

doi:10.1128/jvi.78.23.12762-12772.2004

Cited by 165 publications

(207 citation statements)

References 51 publications

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“…These DNA methylation profiles have been analyzed at the gene and global genome levels in several studies. The de novo methylation of HPV DNA has been interpreted as being a host defense mechanism for silencing viral replication and transcription that is exploited by the virus to maintain a long-latency infection (Doerfler, 1991;Kalantari et al, 2004;Woodman et al, 2007;Fernandez et al, 2009). These dynamic changes in viral DNA methylation profiles during tumorigenesis were highlighted in a study of cultured primary human foreskin keratinocytes transfected with the entire genome of HPV16 or HPV18, which results in its integration into the host cell genome (Steenbergen et al, 1996).…”

Section: Human Papilloma Virusmentioning

confidence: 99%

“…Previous studies of HPV16 DNA methylation have analyzed the entire LCR and L1 regions (Badal et al, 2003(Badal et al, , 2004Kim et al, 2003;Kalantari et al, 2004;Bhattacharjee and Sengupta, 2006;Turan et al, 2007;Hublarova et al, 2009). Even more recent studies have been able to map the DNA methylation of every CpG (DNA methylome) in a collection of human cervical samples corresponding to the different progressive stages of the disease, from asymptomatic carriers to primary cervical carcinomas and several established cervical cancer cell lines (Brandsma et al, 2009;Fernandez et al, 2009).…”

Section: Human Papilloma Virusmentioning

confidence: 99%

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Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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Viruses are associated with 15-20% of human cancers worldwide. In the last century, many studies were directed towards elucidating the molecular mechanisms and genetic alterations by which viruses cause cancer. The importance of epigenetics in the regulation of gene expression has prompted the investigation of virus and host interactions not only at the genetic level but also at the epigenetic level. In this study, we summarize the published epigenetic information relating to the genomes of viruses directly or indirectly associated with the establishment of tumorigenic processes. We also review aspects such as viral replication and latency associated with epigenetic changes and summarize what is known about epigenetic alterations in host genomes and the implications of these for the tumoral process. The advances made in characterizing epigenetic features in cancer-causing viruses have improved our understanding of their functional mechanisms. Knowledge of the epigenetic changes that occur in the genome of these viruses should provide us with markers for following cancer progression, as well as new tools for cancer therapy.

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Section: Human Papilloma Virusmentioning

confidence: 99%

Section: Human Papilloma Virusmentioning

confidence: 99%

Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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“…They are identical to those described in a previous study. 26 PCR was carried out in a 25 ll volume containing 0.2 mM of each of the 4 dNTPs, 10 pmol of each primer, 2 mM MgCl 2 and 1 unit of AmpliTaqGold (Perkin-Elmer). The PCR conditions were 94°C for 1 min, followed by 40 cycles of 94°C for 10 sec, 54°C for 30 sec and 68°C for 1 min with a final extension at 68°C for 7 min.…”

Section: Polymerase Chain Reactions Primers T/a Cloning and Dna Seqmentioning

confidence: 99%

“…in the same position of different HPV genomes either CpGs or meCpGs. [26][27][28] To approach a satisfactory analysis of such mixtures of molecules, we have developed a standardized protocol that we applied here to DNA preparations from oral carcinomas. We treat DNA samples with bisulfite, which converts cytosines into uracils but does not affect methyl cytosine.…”

Section: Design Of the Hpv-16 Dna Methylation Analysismentioning

confidence: 99%

“…When we targeted this approach in past studies to HPV-16 and 18 genomes in cervical and anal lesions, we observed a complex diversity of methylation patterns of HPV genomes both in the comparison of different clinical samples and even within individual clinical samples. [24][25][26][27][28] Among these different patterns, hypermethylation of the HPV-16 and 18 L1 gene and of the HPV-16 long control region (LCR) was common in carcinomas and high-grade lesions, but rare or absent in asymptomatic infections or low-grade lesions, likely a consequence of genomic recombination and aberrant transcription. Here we report that we observed the same meCpG patterns in HPV-16 DNA in oral carcinomas.…”

mentioning

confidence: 99%

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Human papillomavirus‐16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas

Balderas-Loaeza

Anaya‐Saavedra

Ramírez‐Amador

et al. 2007

Intl Journal of Cancer

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Infection with human papillomavirus-16 (HPV-16) is the cause of most anogenital carcinomas. This virus is also detected in about 20% of all head and neck squamous cell carcinomas. While there is strong evidence for a causal etiological role in the case of tonsillar carcinomas, causal association with malignant lesions of the oral cavity is not yet conclusive. Our previous investigations of HPV-16 DNA methylation in anogenital sites have identified hypermethylation of the L1 gene and part of the long control region in many malignant lesions, but rarely in asymptomatic infections and low-grade precancerous lesions. Here, we report hypermethylation of this diagnostically important segment of the viral DNA in 10 out of 12 HPV-16 positive oral carcinomas from Mexican patients. These data indicate epigenetic changes of HPV-16 in oral carcinomas similar to those in anogenital carcinomas, suggesting carcinogenic processes under the influence of HPV-16 in most if not all of these oral malignant lesions. ' 2007 Wiley-Liss, Inc.Key words: papillomavirus; carcinoma; head and neck cancer; oral cavity; DNA methylation; DNA recombination; etiology; progression; Infection with human papillomaviruses (HPVs), notably with high-risk HPV types such as HPV-16 and 18, is a necessary step in the etiology of anogenital cancers, specifically carcinoma of the cervix uteri. This notion is based on epidemiological research that identified a high relative risk of carcinogenic progression associated with high-risk HPV infection, DNA diagnosis that confirmed the presence and transcription of HPV genomes in all cervical carcinomas, and the study of HPV oncoproteins that catalyze a variety of molecular mechanisms that convert normal into malignant cells. [1][2][3][4][5][6] In case of head and neck squamous cell carcinomas (HNSCCs), an HPV dependent etiology is not as consistently confirmed as in anogenital cancers. Approximately 80% of all HNSCCs do not contain HPV genomes, and must therefore originate from HPV independent etiological processes, likely including mutational events triggered by tobacco and alcohol consumption. However, there is extensive evidence that a proportion of all HNSCCs contain DNA of high-risk HPV types. 7-14 Among head and neck sites, squamous cell carcinomas of the tonsils have the strongest statistical support for an HPV dependent etiology. 9,[15][16][17] There is less strength and consistency for a linkage between HPV infection and carcinogenesis at sites of the oral mucosa such as tongue, palate, floor of mouth and gingiva. Nevertheless, epidemiological studies have established statistical evidence for a causal association of HPVs and malignancies even for these oral sites. 9,16 In addition, analysis of some HPV containing oral carcinomas revealed recombination between HPV genomes and cellular DNA as well as HPV oncogene expression, [10][11][12][13][18][19][20] properties that are generally viewed as support of carcinogenic processes under the influence of HPVs. On the basis of these observations one must conclude ...

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The transcriptional response of normal and rheumatoid arthritis synovial fibroblasts to hypoxia

Rey¹,

Izquierdo²,

Usategui³

et al. 2010

Arthritis & Rheumatism

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Objective. Hypoxia is a prominent feature in rheumatoid arthritis (RA) synovium. However, its contribution to the pathogenesis of RA remains unclear. We undertook this study to systematically characterize the changes in gene expression induced by hypoxia in synovial fibroblasts.Methods. We used microarray expression profiling in paired normoxic and hypoxic cultures of healthy synovial fibroblasts (HSFs) and RA synovial fibroblasts (RASFs). We used Student's paired t-test with Benjamini and Hochberg multiple testing correction to determine statistical significance. Validation of microarray data was performed by quantitative real-time reverse transcription-polymerase chain reaction analysis of selected genes. Biologic pathways differentially modulated by hypoxia in RASFs or HSFs were identified using unsupervised Ingenuity Pathways Analysis.Results. Hypoxia induced significant changes in the expression of a large group of genes in both HSFs and RASFs. In RASFs, we observed a lower number of hypoxia-regulated genes and partial differences in their functional categories. The number of differentially expressed genes in RASFs compared with HSFs was significantly increased by hypoxia. Multiple gene sets involved in energy metabolism, intracellular signal transduction, angiogenesis, and immune and inflammatory pathways were significantly modified, the last in both proinflammatory and antiinflammatory directions.Conclusion. These data demonstrate that hypoxia induces significant changes in gene expression in HSFs and RASFs and identify differences between RASF and HSF profiles. The hypoxia-induced gene expression program in synovial fibroblasts identifies new factors and pathways relevant to understanding their contribution to the pathogenesis of chronic arthritis.

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Conserved Methylation Patterns of Human Papillomavirus Type 16 DNA in Asymptomatic Infection and Cervical Neoplasia

Cited by 165 publications

References 51 publications

Viral epigenomes in human tumorigenesis

Viral epigenomes in human tumorigenesis

Human papillomavirus‐16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas

The transcriptional response of normal and rheumatoid arthritis synovial fibroblasts to hypoxia

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