In background information in the article, the authors write that fetal monitoring in the womb is now "limited to noninvasive methods such as measurement of uterine size or anatomic evaluation by fetal sonography. In addition, genetic analysis can be performed on amniotic fluid components " They add that the "cell-free component of the amniotic fluid is discarded after these analyses and is therefore available for research and future clinical applications."

Paige B. Larrabee, M.D., from Tufts-New England Medical Center, Boston, and colleagues analyzed four samples of cell-free amniotic fluid from pregnant women between 20 and 32 weeks' gestation and who had certain conditions that required procedures to reduce an excessive amount of amniotic fluid. The control group in this study was 6 pooled amniotic fluid samples from women at 17 weeks' gestation who were undergoing amniocentesis (removal of amniotic fluid to test for hereditary diseases and congenital defects in the fetus). "After extraction from the normally discarded fraction of amniotic fluid, RNA was amplified twice, labeled, and analyzed using gene expression microarrays." The researchers were able to study the expression of developmental transcripts, such as for certain proteins.

"Preliminary analysis suggests that gene expression changes can be detected in fetuses of different sexes, gestational age, and disease status," the authors report. "Cell-free mRNA in amniotic fluid appears to originate from the fetus and not the placenta." In conclusion the authors write: "The intriguing gene expression differences observed suggest that this technology could facilitate the advancement of human developmental research, as well as the cultivation of new biomarkers for assessment of the living fetus."

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Graham Casey, Ph.D., of the Cleveland Clinic Lerner College of Medicine, Cleveland, and colleagues performed a blinded comparison of conventional DNA sequencing and conversion analysis to identify certain genetic mutations in 89 colorectal cancer cases. The study included patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying certain mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50 years were analyzed from June 2002 to June 2003.

The researchers found that conversion analysis identified all mutations detected by genomic DNA sequencing, plus other mutations, particularly large genomic deletions, yielding an increase of 33 percent (14 of 42) in diagnostic yield of deleterious mutations. Conversion analysis also provided additional information on the deleterious consequence of other sequence changes for an increase of 56 percent (35 of 63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone.

"These results have important implications for genetic testing of individuals for both clinical and research purposes. Testing strategies, whether conversion analysis, as validated herein, or a combination of other approaches, must take into account the highly heterogeneous nature of mismatch repair mutations in colorectal cancer," the authors conclude.

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