We found that the methylation status of the cyclin-dependent kinase inhibitor 2A (<i>P16</i>), Ras association domain family 1 isoform (<i>RASSF1A</i>), adenomatous polyposis coli (<i>APC</i>) and short stature homeobox 2 (<i>SHOX2</i>) genes was significantly correlated with lung cancer in bronchial aspirates.
In the present study, the diagnostic utility of the SHOX2 assay was tested with regard to cytology for different cytological diagnostic categories to assess whether it can complement the cytological examination and the DNA methylation marker panel targeting the gene promoters of adenomatous polyposis coli 1A (APC), cyclin-dependent kinase inhibitor-2A (p16(INK4A)) and Ras association domain family protein 1 (RASSF1A) regarding lung cancer detection in bronchial aspirates.
The aim of this study was to investigate promoter methylation of certain tumor suppressor genes, Cyclin-dependent kinase inhibitor 2A (p16) and Adenomatous polyposis coli (APC), which take part in gastrointestinal tumorigenesis.
In the present study, the methylation patterns of three genes [p16 (INK4A), p15 (INK4B), and adenomatous polyposis coli (APC)] were assessed in patients with gastric adenocarcinoma from Pará state in order to identify possible molecular markers of gastric carcinogenesis.
Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14(ARF), p15(INK4b), p16(INK4a) and survivin.
No deleterious CDKN2a mutations were identified in our families suggesting that CDKN2a mutations are unlikely to predispose PC in FPC families without melanoma.
Sera were analysed by methylation specific PCR (MethyLight PCR) for five genes: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase pi 1 (GSTP1).Beta actin (ACTB) served as control.
Twenty consecutive surgically treated ITAC cases, previously investigated for p16(INK4a) and TP53, were investigated for hMLH1, hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations.
DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP-associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI-H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI-L).
This article traces the historical aspects of hereditary cancer dealing with identification and ultimate molecular genetic confirmation of commonly occurring cancers, particularly of the colon in the case of familial adenomatous polyposis and its attenuated form, both due to the APC germline mutation; the Lynch syndrome due to mutations in mismatch repair genes, the most common of which were found to be MSH2, MLH1, and MSH6 germline mutations; the hereditary breast-ovarian cancer syndrome with BRCA1 and BRCA2 germline mutations; the Li-Fraumeni (SBLA) syndrome due to the p53 mutation; and the familial atypical multiple mole melanoma in association with pancreatic cancer due to the CDKN2A (p16) germline mutation.
The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARbeta) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6-methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1).
As changes in methylation of the following genes occurred marginally, their impact on the formation of colorectal cancer were trivial: adenomatous polyposis coli (APC) (8%, 5/65), Ras association (RalGDS/AF-6) domain family 1A (RASSF1A) (3%, 2/65) and cyclin-dependent kinase inhibitor 2A, alternated reading frame (p14(ARF)) (6%, 4/65).
Of the primary tumors, 73 of 90 (81%) displayed promoter hypermethylation in at least one of the genes studied: 17% (15 of 90) at p16 (CDKN2A); 16% (14 of 90) at O(6)-methylguanine-DNA-methyltransferase; 8% (7 of 90) at GSTP1; 72% (65 of 90) at APC; and 17% (15 of 90) at DAPK.