Disease relevance of Genes, p16

• Chromosome 9p deletions in cutaneous malignant melanoma tumors: the minimal deleted region involves markers outside the p16 (CDKN2) gene [1].
• Detection of homozygous deletions of the cyclin-dependent kinase 4 inhibitor (p16) gene in acute lymphoblastic leukemia and association with adverse prognostic features [2].
• Because the commonly deleted regions at 9p21 includes the p16 (CDKN2A) gene, the status of the p16 gene was further examined in 80 fresh tumors and 19 cell lines of neuroblastoma [3].
• These results show that loss of p16 protein expression is usually observed in Hodgkin's/Reed-Sternberg cells in Hodgkin's disease, frequently associated with p16INK4A gene hypermethylation [4].
• Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T-cell leukemia [5].

High impact information on Genes, p16

• High frequency of p16INK4A gene alterations in hepatocellular carcinoma [6].
• The mts1 gene codes for a 101 amino acid protein which belongs to the subfamily of S100 Ca(2+)-binding proteins and is overexpressed in metastatic cancers as compared to their nonmetastatic counterparts [7].
• It is closely linked to the P16 gene (MTS1) and is homozygously deleted in many tumor cell lines [8].
• This suggests that p16INK4A gene alterations, inc contrast to p53, are not involved in the progression of STS [9].
• Furthermore aberrant P15 protein expression was detected in 85% of patients analyzed with P15 gene abnormalities and abnormal P16 expression in 59% with P16 gene abnormalities [10].

Chemical compound and disease context of Genes, p16

• Because expression of p16INK4A is regulated by methylation of the p16INK4A gene, we examined whether demethylation of the p16INK4A gene by 5-aza-2'-deoxycytidine (5-azadC) could cause the protein expression of VEGF as well as of p16INK4A in human lung cancer cells [11].

Biological context of Genes, p16

• P15 and P16 gene promoter methylation was found in 45% and 29% of patients, respectively [10].
• Germline mutations in the p16 (CDKN2A) gene have been reported in at least a quarter of such families [12].
• Two mutations in the CDKN2A (p16) gene were detected, including a novel base change AAC-->ATC (Asn to Ile) at codon 71, that also changes the codon 85 of the alternative reading frame gene p14(ARF) from CAA to CAT (Gln to His) [13].
• The p16INK4A gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene [14].
• Transient transfection of the p16INK4A gene into SCLC cells resulted in exogeneous p16INK4A protein expression and dephosphorylation of endogenous retinoblastoma (RB) protein [15].

Anatomical context of Genes, p16

• The cyclin-dependent kinase 4 inhibitor (CDKN2) gene, which maps to 9p21, has been implicated by the finding of a high frequency of biallelic deletions in leukemic cell lines [16].
• Frequent p16INK4 (MTS1) gene inactivation in testicular germ cell tumors [17].
• The cyclin kinase inhibitor p16, encoded by the CDKN2A gene, suppresses the transformation of mouse embryonic fibroblasts by oncogenic RAS [18].
• Our results demonstrated that: (1) the biallelic loss of p16INK4A gene is strictly related to a specific immunophenotype, namely ALL of T-cell lineage; (ii) no significant correlation exists between alterations at chromosome 9p level and the homozygous deletions of p16INK4A gene; and (iii) p18 gene was not deleted in the examined cases [19].
• Establishment of a novel human B-cell line (OZ) with t(14;18)(q32;q21) and aberrant p53 expression was associated with the homozygous deletions of p15INK4B and p16INK4A genes [20].

Associations of Genes, p16 with chemical compounds

• Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16) [21].
• These data indicate that flavopiridol shows cell type specific inhibition and possibly acts in a more compensatory manner for endogenous p16INK4a function in tumor cells having the aberrations of p16INK4a gene [22].
• RESULTS: 5-aza-dC induced the demethylation of p16INK4A gene promoter [23].
• DNA methylation status of p16INK4A gene promoter was assayed by bisulfite modification and sequencing [23].

Gene context of Genes, p16

• Analysis of CpG island hypermethylation in EAC has thus far been limited to the CDKN2A (p16) gene [24].
• Two high-risk melanoma susceptibility genes-CDKN2A and CDK4-have been identified to date, with a third gene p14(ARF) also being suspected of playing a role [25].
• Moreover, the absence of MTAPase activity seems to be a valuable marker of p16INK4A gene inactivation, thus indicating that the deleted chromosomal area on 9p21 very frequently involves the MTAPase gene [19].
• On the other hand, genetic alterations of the cyclin D1 and p16INK4A genes were not so frequent, but appeared to be associated with the aggressive behavior of the tumor, which suggests that disruption of the cell cycle-related genes results in the progression of HCC [26].
• Among the four CDK inhibitor genes, alterations of only the p16INK4A gene were found in 8 out of 34 (24%) cell lines, and all eight cell lines having a p16INK4A gene alteration had an alteration of either the K-ras of p53 gene [27].

Analytical, diagnostic and therapeutic context of Genes, p16

• Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases [28].
• Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity [29].
• To increase the sensitivity of detection, a two-step methylation-specific PCR approach was used to analyze the methylation status of the promoter/exon 1 regions of both p14ARF and p16INK4A genes [30].

References