(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.
p16INK4a, a cell cycle inhibitor that inhibits cyclin-dependent kinase 4 (cdk4) and cdk6, has been found as the tumor suppressor gene and is frequently deleted, methylated or mutated in many malignancies.
p16INK4A, a specific inhibitor of cyclin-dependent kinase (cdk)4 and cdk6, is a candidate tumor suppressor in malignancies with wild-type retinoblastoma (Rb).
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.