Screening of urine identifies PLA2G16 as a field defect methylation biomarker for prostate cancer detection.

BackgroundProstate cancer (PC) is a multifocal disease. DNA methylation alterations are not restricted to the immediate peritumor environment, but spatially widespread in the adjacent and distant histologically normal prostate tissues. In the current study, we utilized high-throughput methylation arrays to identify epigenetic changes in the urine from men with and without cancer.Design, setting, and participantsDNA urine samples were enriched for methylated fragments using MBD methyl-binding antibodies and applied to high density CytoScanHD arrays. Significant loci were validated using quantitative pyrosequencing and binary logistic regression modeling applied to urine sample analyses in a training (n = 83) and validation approach (n = 84). Methylation alterations in prostate tissues using pyrosequencing at the PLA2G16 locus were examined in 38 histologically normal specimens from men with (TA, n = 26) and without (NTA, n = 12) cancer and correlated to gene expression.ResultsMethylation microarrays identified 3,986 loci showing significantly altered methylation in the urine samples from patients with PC compared to those without (TA vs NTA; pConclusionPLA2G16 methylation defines an extensive field defect in histologically normal prostate tissue associated with PC. PLA2G16 methylation in urine and prostate tissues can detect the presence of PC

Magnetostratigraphy and biostratigraphy of ODP Leg 105 sites and DSDP Hole 12-112

During Ocean Drilling Program (ODP) Leg 105, three sites (Sites 645 through 647) were drilled in Baffin Bay and the Labrador Sea to examine the tectonic evolution and the climatic and oceanic histories of this region. Biostratigraphic and magnetostratigraphic results vary at each site, while stratigraphic resolution depends on the limited abundance of marker species and the completeness of the paleomagnetic record. Because of the paucity of planktonic microfossils and the poor paleomagnetic record signatures, stratigraphic determinations at Site 645 often rely on defining minimum temporal constraints on specific samples or stratigraphic intervals. The completed stratigraphy indicates that the sedimentary sequence recovered at Site 645 is early Miocene to Holocene in age. The magnetostratigraphy and biostratigraphies are better defined at Sites 646 and 647 in the Labrador Sea. Site 646 generally contains a well-developed magnetostratigraphy and calcareous microfossil biostratigraphy. This biostratigraphy is based on calcareous nannofossils and planktonic foraminifers typical of the North Atlantic Ocean. Siliceous microfossils are also present at Site 646, but they are restricted to upper Pliocene through Holocene sediments. The stratigraphic sequence recovered at Site 646 is late Miocene to Holocene in age. Based primarily on the calcareous nannofossil stratigraphy, the sequence recovered at Site 647 consists of lower Eocene to lower Oligocene, lower Miocene, upper Miocene, and upper Pliocene through Holocene sediments. Three hiatuses are present in this sequence: the older hiatus separates lower Oligocene sediments from lower Miocene sediments, another hiatus separates lower Miocene sediments from upper Miocene sediments, and the youngest one separates upper Miocene from upper Pliocene sediments. A magnetostratigraphy is defined for the interval from the Gauss/Matuyama boundary through the Brunhes (Clement et al., this volume). Both planktonic foraminifers and siliceous microfossils have restricted occurrences. Planktonic foraminifers occur in Pliocene and younger sediments, and siliceous microfossils are present in lower Miocene and lower Oligocene sediments. The near-continuous Eocene through lower Oligocene sequence recovered at Site 647 allows the calcareous nannofossils and diatom stratigraphies at this site to act as a Paleogene stratigraphic framework. This framework can be compared with the stratigraphy previously completed for DSDP Site 112