RGD Reference Report - Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia. - Rat Genome Database

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Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia.

Authors: Kang, S  Kim, J  Kim, HB  Shim, JW  Nam, E  Kim, SH  Ahn, HJ  Choi, YP  Ding, B  Song, K  Cho, NH 
Citation: Kang S, etal., Diagn Mol Pathol. 2006 Jun;15(2):74-82.
RGD ID: 2296054
Pubmed: PMID:16778587   (View Abstract at PubMed)

The cell cycle inhibitor, p16INK4a may be a useful surrogate biomarker of cervical intraepithelial neoplasia (CIN); however, there is currently no consensus of p16INK4a genetic alterations throughout the multiple step process of CIN. Our goal was to identify the methylation frequency of p16INK4a in each step of CIN that is associated with human papillomavirus (HPV) infection, using several different detection methods of p16INK4a methylation to correlate the data. The present study included a total of 43 patients, including 38 with CIN, and 5 normal patients. Three different methods were used to detect hypermethylation of CpG islands, methylation-specific PCR (MSP) amplification of different primer sets of M1, M2, and M3, pyrosequencing of each forward primer region, and immunohistochemistry of p16INK4a. Analysis of MSP showed that 20 of the 38 CIN patients (52.6%) revealed hypermethylation in at least 1 primer set of the p16INK4a promoter. A complete loss of p16INK4a protein expression was observed in 11 cases (28.9%). There was no observed association of methylation of the p16INK4a gene with either CIN grading (P=0.0698) or HPV status (P=0.2811): specifically 42.9% (3/7) was found in CIN 1, 57.1% (8/14) in CIN 2, and 52.9% (9/17) in CIN 3. In concordance with immunohistochemistry results, hypermethylation of the p16INK4a promoter was significantly correlated with a lack of p16 protein expression (P=0.0145). All positive peaks from pyrosequencing matched the MSP results, which ranged from 6.3% to 24.5%. In conclusion, p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervix uteri carcinoma in situ  IDA 2296054DNA:hypermethylationRGD 
cervix uteri carcinoma in situ  ISOCDKN2A (Homo sapiens)2296054; 2296054DNA:hypermethylationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)

Genes (Mus musculus)
Cdkn2a  (cyclin dependent kinase inhibitor 2A)

Genes (Homo sapiens)
CDKN2A  (cyclin dependent kinase inhibitor 2A)


Additional Information