External pancreatic duct stents inserted after resection of pancreatic headtumors provide unique access to pancreatic juice analysis of genetic andmetabolic components that may be associated with peri-ampullary tumorprogression. For this pilot study, portal venous blood and pancreatic juicesamples were collected from 17 patients who underwent pancreaticoduodenectomyfor peri-ampullary tumors. Portal vein circulating tumor cells (CTC) wereisolated by high-speed fluorescence-activated cell sorting (FACS) and analyzedby quantitative reverse transcription polymerase chain reaction (RT-PCR) forK-RAS exon 12 mutant gene expression(K-RASmut). DNA, chromatin, and histone acetylated activechromatin were isolated from pancreatic juice samples by chromatinimmunoprecipitation (ChIP) and the presence of K-RASmut andother cancer-related gene sequences detected by quantitative polymerase chainreaction (PCR) and ChIP-Seq. Mutated K-RAS gene was detectablein activated chromatin in pancreatic juice secreted after surgical resection ofpancreatic, ampullary and bile duct carcinomas and directly correlated with thenumber of CTC found in the portal venous blood (P = .0453).ChIP and ChIP-Seq detected acetylated chromatin in peri-ampullary cancer patientjuice containing candidate chromatin loci, including RETproto-oncogene, not found in similar analysis of pancreatic juice fromnon-malignant ampullary adenoma. The presence of active tumor cell chromatin inpancreatic juice after surgical removal of the primary tumor suggests thatviable cancer cells either remain or re-emerge from the remnant pancreatic duct,providing a potential source for tumor recurrence and cancer relapse. Therefore,epigenetic analysis for active chromatin in pancreatic juice and portal venousblood CTC may be useful for prognostic risk stratification and potentialidentification of molecular targets in peri-ampullary cancers.

How organisms retain a memory of ancestral environmental exposure is a phenomenon that is still poorly understood. Recently published work by our group and others, regarding environmentally induced transgenerational effects, have identified an array of mechanisms, with a particular focus on histone modifications, that shed some light on the underlying epigenetic processes driving long-term generational effects.

How the epigenome of one cell type is remodeled during reprogramming into another unrelated type of cell remains unclear. Overexpression of transcription factors in somatic cells enables the induction of induced pluripotent stem cells (iPSCs). This process entails genome-wide remodeling of DNA methylation, chromatin, and transcription. Recent work suggests that the number of active X chromosomes present in a cell influences remodeling of DNA methylation during somatic cell reprogramming to mouse iPSCs. Female iPSCs with 2 active X chromosomes display global DNA hypomethylation, whereas male XY iPSCs show DNA methylation levels similar to the somatic cells they are derived from. Global DNA methylation erasure in female iPSCs takes place genome-wide and involves repression of DNA methyltransferases. However, on loss of one X chromosome, female iPSCs acquire a DNA methylation landscape resembling that of XY iPSCs. Therefore, it is the X chromosome dosage that dictates global DNA methylation levels in iPSCs. Here, we discuss the evidence that links X chromosome dosage with the regulation of DNA methylation in pluripotent stem cells. We focus on iPSCs reprogramming studies, where X chromosome status is a novel factor impacting our understanding of epigenetic remodeling.