CDKN2A is a tumor suppressor gene and is frequently inactivated in human cancers by hypermethylation of its promoter. However, the role and diagnostic value of CDKN2A methylation in esophageal cancer (EC) remains controversial. Therefore, we performed a meta-analysis, including data from 42 articles (2656 ECs, 612 precancerous lesions, and 2367 controls). A significant increase in the frequency...

We tested whether methylation profiles generated by real-time methylation-specific PCR (MSP) can be useful in differentiating benign, reactive mesothelial cell proliferation (RM) from malignant mesothelioma (MM). Forty-two of the 63 cases (67%) yielded informative results for RARbeta2, GPC3, CDKN2A (p16), TERT, and CCND2 (cyclinD2) gene methylation. DNA methylation of any gene was observed in m...

CDKN2A coding region germline variants are associated with pancreatic adenocarcinoma (PC) susceptibility. Recently, we described functional germline 5'UTR CDKN2A variants from melanoma patients affecting the post-transcriptional regulation of p16INK4a mRNA that is dependent, at least in part, on an Internal Ribosome Entry Site (IRES) in the 5'UTR region. Here we describe a 5'UTR c.-201_-198deli...

In order to gain a better understanding of the underlying biology of squamous cell carcinoma (SCC), we tested the hypothesis that SCC originating from different organs may possess common molecular alterations. SCC samples (N = 361) were examined using clinical-grade targeted next-generation sequencing (NGS). The most frequent SCC tumor types were head and neck, lung, cutaneous, gastrointestinal...

The strongest known epidemiologic risk factor for melanoma is a large number of melanocytic nevi (Swerdlow and Green, 1987), whereas the most important genetic risk factor is germline mutation of the CDKN2A gene, which encodes the cell cycle inhibitor p16 (Kamb et al, 1994; Nobori et al, 1994). CDKN2A mutations exist in some melanoma-prone families (reviewed in Hayward, 1996; Foulkes et al, 199...

Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germline CDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neop...

AIM Gastric cancer is a major health problem and current treatment lacks lasting effect. Targeted therapy for gastric cancer with specific genetic background is in urgent need. METHODS We have studied The Cancer Genomic Atlas (TCGA) and The Genomics of Drug Sensitivity in Cancer (GDSC) databases to reveal genes with high frequency of mutation and possible sensitive compound against such gene ...

AIMS It has been shown previously (by immunohistochemistry) that gastric adenocarcinomas harbouring Epstein-Barr virus (EBV) frequently lose p16 protein. This study aimed to examine the mechanisms of inactivation of the CDKN2A gene and correlate the results with clinicopathological features. METHODS Methylation specific polymerase chain reaction was used to detect CDKN2A promoter methylation ...

High-risk human papillomaviruses (HPV) cause cancer at multiple distinct anatomical locations. Regardless of the tissue of origin, most HPV positive (HPV+) cancers show highly upregulated expression of the p16 product of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. Paradoxically, HPV+ tumor cells require continuous expression of this tumor suppressor for survival. Thus, restoration o...

Cyclin-dependent kinase inhibitors CDKN2B and CDKN2A are tumor suppressor genes that are frequently dysregulated in a variety of cancers. Aberrant regulation via DNA hypermethylation causes gene silencing. Arsenic trioxide has been successfully used to treat malignant, hematopoietic diseases and is known to act by induction of apoptosis and inhibition of cellular proliferation. However, arsenic...