Promoter hypermethylation profile of ovarian epithelial neoplasms.

Purpose: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis.

Experimental Design: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARbeta, E-cadherin,H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR.

Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces programmed cell death (apoptosis) in various cancer cells but not in normal cells. TRAIL is known to bind to 4 different receptors, 2 proapoptotic (DR4 and DR5), and 2 potentially antiapoptotic receptors lacking death domains (DcR1 and DcR2). Aberrant promoter methylation and resultant silencing of tumor suppressor genes play an important role in the pathogenesis of many tumor types.

Establishment and Validation of Quantitative Real-time PCR Assay for Aberrant Methylation of Gene in Breast and Lung Carcinoma.

Background: 14-3-3σ gene has been shown to be responsible for G2 cell cycle checkpoint control by p53 in response to DNA damage in human cells. In order to increase the potential utility of 14-3-3σ gene as a molecular marker in tumor analysis and prognosis, we established and validated a quantitative real-time MSP assay and correlated our findings with the standard MSP assay.

Materials And Methods: We examined the expression of 14-3-3 σ gene by reverse transcription PCR (RT-PCR) in breast and lung cancer cell lines and control non-malignant tissue samples.

Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers.

An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor beta-2 (RARbeta-2), CDH13 (H-cadherin), p16(INK4a) (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens.

Epigenetic down-regulation of death-associated protein kinase in lung cancers.

Purpose: Death-associated protein kinase (DAPK) is a pro-apoptotic serine/threonine kinase involved in apoptosis. Aberrant methylation of DAPK was reported in lung cancers by methylation-specific PCR. However, we were unable to relate methylation with gene silencing with the same methodology.

Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer.

Aberrant methylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of lung cancers. There are major smoke exposure, histology, geography and gender-related changes in non-small cell lung cancer (NSCLC). We investigated smoking-related, histologic, geographic and gender differences in the methylation profiles of resected NSCLCs.

Establishment and validation of real-time polymerase chain reaction method for CDH1 promoter methylation.

Aberrant methylation of the promoter region has emerged as the major mechanism for silencing tumor suppressor genes. However, for some genes, such as E-cadherin (CDH1), methylation and protein expression demonstrate considerable heterogeneity, making correlations difficult. We compared methylation and protein expression status of CDH1 in 56 primary breast carcinomas using semiquantitative assays.

Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines.

Aberrant promoter methylation of tumor suppressor genes has not been fully investigated in pediatric tumors. Therefore, we examined the methylation status of nine genes (p16(INK4A), MGMT, GSTP1, RASSF1A, APC, DAPK, RARbeta, CDH1 and CDH13) in 175 primary pediatric tumors and 23 tumor cell lines using methylation-specific PCR. We studied the major forms of pediatric tumors--Wilms' tumor, neuroblastoma, hepatoblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma and acute leukemia.

Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells.

Mesotheliomas are tumors arising from mesothelial cells and are associated with asbestos exposure and approximately 50% contain simian virus 40 (SV40) DNA sequences. SV40 infection of human mesothelial cells (HM) causes early cellular immortalization and late transformation. Aberrant methylation is a major mech-anism for loss of function of tumor suppressor genes (TSGs).

Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas.

Expression of the cadherin family member CDH13 (H-cadherin) is reduced in several human tumors, and it has been hypothesized that this gene functions as a tumor suppressor gene. Previously, we reported that the 5' region of CDH13 is frequently methylated in breast and lung cancers. Here we confirmed the promoter activity of 5' region of CDH13 by luciferase assay and examined its aberrant methylation in colorectal cancers, cell lines, and adenomas.

Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features.

Purpose: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings.

Experimental Design: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer.