(3) Methylation of the CpG islands of p16(INK4a) and p14(ARF) was detected in 47.9% (23/48) of gastric cancers, while methylation was observed only in 2 of 48 gastric tissues neighboring the cancer with a significant difference (P < 0.01).
Cancer genomics analysis revealed that 36 of the most differentially expressed mRNAs were involved in a pancreatic cancer network and were associated with many critical mutated genes such as TP53, KRAS, SMAD4, and CDKN2A.
CDKN2A and PTEN mutations were clearly associated with increasing tumor malignancy (occurring in 0% of grade 2 tumors, 14.3% and 4.8% respectively of grade 3 tumors, and 27.3% and 30.3% respectively of grade 4 tumors) and were observed at substantially higher rates among astrocytomas.
p16ink4 and pRb, two components of a key G1/S regulatory pathway, and tumor suppressors commonly targeted in oncogenesis, are among the candidates for gene therapy of cancer.
A high degree of methylation in USP10 and p14ARF CpG islands was found by methylation specific PCR analysis in cancer than in normal tissues and cells.
A significant increase in the frequency of CDKN2A methylation was identified during EC carcinogenesis: cancer vs. controls, odds ratio (OR) = 12.60 (95 % CI, 8.90-17.85); cancer vs. precancerous lesions, OR = 2.89 (95% CI, 2.20-3.79); and precancerous lesions vs. controls, OR = 7.38, 95% (CI, 4.31-12.66).
A survival analysis by p16 status, p53 status, Union for International Cancer Control stage and main treatment modality demonstrated that only p16 status was related to better prognosis in terms of overall survival and disease-specific survival (3-year overall survival, 87 vs. 62%, P = 0.02; 3-year disease-specific survival, 90 vs. 62%, P = 0.02).
A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far.
According with our results, methylation of p16(INK4a) promoter may be involved in the bladder cancer genesis and the presence of p16(INK4a) methylated in serum of these patients could be useful in the cancer diagnosis with values of sensitivity, specificity and positive predictive value of 0.226, 0.950 and 0.98, respectively.
Additionally, senescence via a p53- and p16(INK4A)-dependent mechanism can be induced by the over- or under-stimulation of certain signalling pathways that are involved in cancer.
Additionally, the mining of an online dataset (The Cancer Genome Atlas) revealed codeletions of PTEN and TP53 and/or CDKN2A/p14ARF in ~25% of human MMs, indicating that cooperative losses of these genes contribute to the development of a significant proportion of these aggressive neoplasms and suggesting key target pathways for therapeutic intervention.
Adenovirus-Mediated Expression of the p14 Fusion-Associated Small Transmembrane Protein Promotes Cancer Cell Fusion and Apoptosis In Vitro but Does Not Provide Therapeutic Efficacy in a Xenograft Mouse Model of Cancer.
After further stratification of the cancer group into different clinical-pathologic parameters, there were significant associations in the sex and LN involvement groups in MK gene; alcohol consumption group in p16 gene; age and cell differentiation groups in p21 gene; age and tumour location groups in p53 gene; but we fail to find any significant association with IL-4 gene polymorphisms.
After stratification by race, p16(INK4) in European-Americans and BRCA1 hypermethylation in African-Americans were associated with family history of cancer (OR 3.8; 95%CI: 1.21-12.03 and OR 6.5; 95%CI: 1.33-31.32, respectively).