Carcinogenesis of cervical cancer has been investigated, and p16(INK4a) overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein.
CDKN2 is not deleted with high frequency in primary breast carcinomas, and the p16 gene does not play a role in breast carcinogenesis via this mechanism.
A larger study on VIN lesions and genetic coding is suggested to further investigate the role of p16INK4, Rb, and other factors in tumorigenesis and progression of vulvar cancers.
A strong correlation was observed between the promoter methylation of RASSF1A gene but not p16 gene (both frequently inactivated by promoter methylation in lung cancer) and expression of DeltaDNMT3B4 in primary lung cancer, suggesting a role of DeltaDNMT3B in regulating promoter-specific methylation of common tumor suppressor genes in tumorigenesis.
A tumor suppressor gene, p16, was found to harbor promoter hypermethylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation was important for colorectal tumorigenesis.
A tumor suppressor gene, p16, was found to harbor promoter methylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation may be important for gastric tumorigenesis.
Abnormal hypermethylation of the CDKN2A (p14ARF and p16INK4a) gene can lead to repression of gene expression and contribute to carcinogenesis and tumor progression.
Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis.
Also suggested is that p16 has no role in the specific malignant transformation step from immortal premalignant lesions during the carcinogenesis of HPV-initiated cervical cancers.
Alterations of the p16INK4 gene were detected in 6 (2 insertions and 4 homozygous deletions) of 22 metastatic non-small cell lung cancers (NSCLCs; 27%), but none were detected in 25 primary NSCLCs, 15 primary small cell lung cancers (SCLCs), or 9 metastatic SCLCs, indicating that mutation in the p16INK4 gene is a late event in NSCLC carcinogenesis.
Although limited to date, previous studies have suggested that NF1 (17q), NF2 (22q), p16 (9p), and EGFR (7p) alterations may be involved in MPNST tumorigenesis.