Hypomethylation of long interspersed nuclear element-1 in hepatocellular carcinomas.

Recent studies have revealed the epigenetic alterations are involved in hepatocarcinogenesis. However, the function of long interspersed nuclear element-1 hypomethylation in hepatocellular carcinomas, and relationship among other clinicopathologic features, and genetic and epigenetic alterations, including CpG island hypermethylation, have not been studied. We determined long interspersed nuclear element-1 methylation, a marker of global methylation, in 57 tumor and nonneoplastic samples, including 24 from high-risk and 33 from low-risk countries. We compared methylation levels of long interspersed nuclear element-1 with eight CpG islands including p16, cyclooxygenase-2, T-type calcium channel, and estrogen receptor genes, and MINT31, MINT1, MINT2, and MINT27, as well as CpG island methylator phenotype and p53 gene mutation. Most hepatocellular carcinomas samples (88%) showed hypomethylation of long interspersed nuclear element-1, with a mean level of global methylation of 58+/-14 compared to 77+/-6 in nonneoplastic hepatic tissue (P<0.001). Levels of long interspersed nuclear element-1 hypomethylation differed depending on geographic location (P=0.02), status of hepatitis (P=0.01), hypermethylation of p16, estrogen receptor and MINT2 (P=0.01, 0.002, and 0.045, respectively), CpG island methylator phenotype-positive status (P=0.006), and p53 gene mutation (P=0.04). In conclusion, environmental factors such as geographic location and hepatitis status contribute to hepatocarcinogenesis through global hypomethylation. In hepatocellular carcinomas, hypermethylation of CpG islands, and CpG island methylator phenotype status seems to correlate with levels of long interspersed nuclear element-1 hypomethylation.

Community sexually transmitted infection services are good enough: a qualitative study of clients' experiences.

BACKGROUND: Lewisham in South East London, UK has high rates of sexually transmitted infection (STI), termination of pregnancy and teenage conception. Greater community provision of STI services has been proposed nationally to address the current sexual health crisis but concern has been expressed about their quality. Lewisham Community Sexual and Reproductive Health (S&RH) Department has been providing testing and treatment for uncomplicated STI since 2002. OBJECTIVE: To explore the experiences of clients using a community STI service for testing and treatment. METHODS: A qualitative study involving semi-structured interviews with 16 clients diagnosed with a STI and attending a South East London community STI service for treatment. RESULTS: Three main themes emerged during the analysis. The environment in sexual health clinics is important in determining the degree of stigma experienced by these clients. Easy access to a STI service is an important factor in determining clients' choice of services. This local community STI service provided an acceptable and satisfactory service to these clients requiring uncomplicated STI treatment. CONCLUSIONS: This study demonstrates that a community STI service is acceptable to clients using a community S&RH service. More research is urgently needed to determine whether community STI treatment would be acceptable to client groups who do not currently use such a service.

Validation of a Chromosomal Microarray for Prenatal Diagnosis Using a Prospective Cohort of Pregnancies with Increased Risk for Chromosome Abnormalities.

AIM: Validation of a chromosomal microarray for improved prenatal diagnosis for chromosomal abnormalities among high-risk pregnancies. METHODS: A cohort of 213 pregnancies was investigated by chromosomal microarray and the results were compared with quantitative fluorescent polymerase chain reaction (QF-PCR), karyotype, and 850K single-nucleotide polymorphism microarray results. The detection limit of mosaicism was determined by assaying different trisomy mosaic constructs down to ∼12%. Imprecision estimates from replicates of mean log2 ratio values for a 200 kb deletion and 400 kb duplication were determined by evaluating the coefficient of variation (CV%). RESULTS: Excluding pregnancies with aneuploidy, the chromosomal microarray detected 19/213 (8.9%) pregnancies with copy number abnormalities. These were classified as pathogenic in 11/213 (5.2%) cases, as variants of uncertain significance in 4/213 (1.9%) cases, and as likely benign in 4/213 (1.9%) cases. In 15/213 (7.0%) pregnancies, these abnormalities were not detectable by karyotype. Importantly, 8/11 (72.7%) of the pathogenic abnormalities detected by chromosomal microarray were only detectable by this modality. There were no false-positive results and only eight false-negative results. The chromosomal microarray showed excellent sensitivity (96.2%) and specificity (100.0%). The lower detection limit for mosaicism was ∼12%. Imprecision for the 0.2 Mb deletion (11.6 CV%) and 0.4 Mb duplication (5.9 CV%) was very low. CONCLUSION: This chromosomal microarray showed excellent diagnostic performance with improved detection rates compared to karyotyping for prenatal diagnosis of clinically relevant fetal chromosomal abnormalities.

Frequent loss of heterozygosity of chromosome 1q in esophageal adenocarcinoma: loss of chromosome 1q21.3 is associated with shorter overall survival.

BACKGROUND: Previous microarray expression profiling studies have shown that genes located on chromosome region 1q21-23 were down-regulated in the progression of Barrett esophagus to esophageal adenocarcinoma and that, among patients with the latter condition, these genes were differentially expressed between responders and nonresponders of preoperative chemoradiation therapy. It was unclear whether this difference was due to loss of heterozygosity (LOH) or to other genetic alterations at this locus. METHODS: The status of chromosome 1q LOH was retrospectively evaluated in formalin-fixed, paraffin-embedded pretreatment biopsy specimens from 33 patients with locally advanced esophageal adenocarcinoma who were treated with preoperative neoadjuvant therapy, and the findings were correlated with clinicopathologic features and overall survival duration. LOH was determined by polymerase chain reaction analysis of 7 dinucleotide microsatellite markers that spanned chromosomal region 1q21-23. RESULTS: Allelic loss of chromosome 1q with any marker was found in 66% of tumors; 58% of tumors demonstrated loss of chromosome 1q21, and 45% of tumors demonstrated loss of chromosome 1q23. Patients with loss of chromosome 1q21.3 had shorter overall survival duration than patients without loss of chromosome 1q21.3 (P = .02). The difference in survival with loss of the chromosome 1q21.3 region was also found to be significant in a subset of patients with incomplete pathologic response to preoperative therapy (P = .024). CONCLUSIONS: Loss of chromosome 1q was a frequent finding in esophageal adenocarcinoma cases, and loss of the 1q21.3 region was associated with shorter overall survival duration.