ArticleBMC cancer2007
Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas.
Article in BMC cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Pooled it
- p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis.Cancer treatment reviews · 2009Pooled it
- Methylation of p16 ink4a promoter is independent of human papillomavirus DNA physical state: a comparison between cervical pre-neoplastic and neoplastic samples.Memorias do Instituto Oswaldo Cruz · 2018Article
- Role of quantitative p16International journal of cancer · 2017Article
- DNA methylation similarities in genes of black South Africans with systemic lupus erythematosus and systemic sclerosis.Journal of biomedical science · 2015Article
- TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.The Journal of clinical investigation · 2015Article
- p16(INK4a) expression in retinoblastoma: a marker of differentiation grade.Diagnostic pathology · 2014Article
- Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population.Molecular biology reports · 2012Article
- p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors.Oncogene · 2011Review
- Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Promoter methylation of p16(INK4A), hMLH1, and MGMT in liquid-based cervical cytology samples compared with clinicopathological findings and HPV presence.Infectious diseases in obstetrics and gynecology · 2011Article
- Expression and methylation pattern of p16 in neuroblastoma tumorigenesis.Pathology oncology research : POR · 2010Article
- Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer.BMC medical genomics · 2009Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHigh risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25-57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas
methodsMethylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16ink4a was analyzed by RT-PCR and by immunohistochemical technique.
resultsThe extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors.
conclusionHypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16ink4a. Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16ink4a is a feature of cervical carcinomas.
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