Since becoming clinically available in 2011, the use of noninvasive prenatal testing (NIPT) to screen for fetal aneuploidy has continued to increase. However, it has been questioned whether the education of patients undergoing NIPT consistently meets informed consent standards. We sought to evaluate patients' basic understanding of NIPT, such as conditions assessed and accuracy. In addition, we investigated patient self-assessment of NIPT knowledge and satisfaction with the testing process. We distributed an anonymous paper survey to pregnant women during prenatal visits following a negative NIPT result. The survey assessed patient NIPT knowledge, gathered pregnancy-specific and demographic information, and allowed respondents to rank their basic understanding of NIPT and provide written feedback about the testing process. A total of 95 completed and 3 partially completed surveys were returned. Participants scored lowest on knowledge questions involving whether a negative NIPT result ensures a healthy baby or eliminates the possibility of Down syndrome. Most perceived themselves to have a good basic understanding of NIPT and two-thirds of the written feedback proposed no changes to NIPT administration. Overall, most patients appear satisfied with their understanding of NIPT and the testing process, yet they may not fully appreciate the limitations of this screening method.
Aberrant expression of developmentally silenced genes, characteristic of tumor cells and regenerating tissue, is highly correlated with increased cell proliferation. By modeling this process in vitro in synthetic nuclei, we find that DNA replication leads to deregulation of established developmental expression patterns. Chromatin assembly in the presence of adult mouse liver nuclear extract mediates developmental stage-specific silencing of the tumor marker gene alpha-fetoprotein (AFP). Replication of silenced AFP chromatin in synthetic nuclei depletes sequence-specific transcription repressors, thereby disrupting developmentally regulated repression. Hepatoma-derived factors can target partial derepression of AFP, but full transcription activation requires DNA replication. Thus, unscheduled entry into S phase directly mediates activation of a developmentally silenced gene by (i) depleting developmental stage-specific transcription repressors and (ii) facilitating binding of transactivators.Cellular commitment, differentiation, and specificity are determined primarily by the interaction of protein complexes with chromatin DNA. This gene-regulatory programming is challenged during each cell cycle by passage of the replisome during DNA synthesis. DNA replication may facilitate competition between transiently disrupted histones and transacting factors at the replication fork, potentially changing established chromatin structure and gene expression patterns (2,7,20,29,59). During tumorigenesis, terminally differentiated cells that have withdrawn from the cell cycle are induced to resume cycling, often through functional inactivation of tumor suppressor genes such as Rb and INK4a (30,33). This cyclic disruption of chromatin structure provides a fertile environment, similar to that which exists during fetal development, for altering gene expression patterns. Aberrant adult activation of genes normally expressed only in the fetus is characteristic of many tumors (reviewed in references 31 and 39). For example, a hepatoma marker gene, alpha-fetoprotein (AFP), is transcriptionally repressed shortly after birth (reviewed in reference 52) and is reexpressed in mature hepatocytes only when they leave G 0 quiescence and begin cycling following partial hepatectomy or during hepatocellular carcinoma (HCC) (42; reviewed in reference 52). Expression of AFP is therefore closely linked to cell cycle progression; the renewal of DNA replication following transition from quiescence to S phase may play an epigenetic role in modulating gene expression.The relative local concentration of transacting factors at the time of replication can determine whether a given chromatin structure is maintained or converted to an alternate conformation (17, 58). Modulating the balance of repressors and activators present during replication could be achieved through a variety of mechanisms, including functional inactivation of repressors and activation of transcription factors. Alternatively, the availability of transactivators could be controlled by s...
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