Manuela Concu

Rapid clearance of mRNA for PLAC1 gene in maternal blood after delivery.

Objective: To evaluate (1) whether the presence of mRNA for the specific trophoblast gene PLAC1 in maternal whole blood is pregnancy-specific, and (2) whether delivery would result in the clearance of mRNA from maternal blood. Methods: Sixteen pregnant women at term (41 completed weeks’ gestation) were enrolled in the study. Blood samples were obtained before the onset of labor and 24 h after delivery. Eight healthy donors (3 males and 5 non-pregnant women) were used as controls. Total RNA was extracted by means of ABI Prism 6100. A quantitative evaluation was obtained by means of real-time PCR. Wilcoxon test was used to evaluate differences between time intervals. Results: Median concentrations of PLAC1 mRNA relative to the standardization curve (see below) were 44 (2.9–675) ng/ml and 0.48 (0.05–10.7) ng/ml respectively for pre- and post-delivery samples (p value <0.001). Male and non-pregnant female controls did not show any signal of cDNA amplification. Conclusion: mRNA transcripts from a placenta-expressed specific gene are detectable in maternal blood and rapidly disappear after delivery. Such an mRNA provides a gender-independent marker for non-invasive prenatal gene expression profiling, and can open new perspectives to monitor those conditions associated to trophoblast damage as well as preeclampsia.

FHIT oncosuppressor gene expression profile in human anal cancers

The FHIT gene, a member of the histidine triad gene family, is a tumor suppressor gene exhibiting deletions in the majority of human cancers. Aberrant transcripts of this gene have been found in about 50% of esophageal, stomach and colon carcinomas. Little is known about the molecular mechanisms involved in malignant transformation of the lining cells of the anus. In this study FHIT gene expression was investigated in this particular kind of human cancer. FHIT expression was comparatively analyzed at the mRNA level, by RT-PCR, in squamous anal cancers, normal anal tissue and peripheral blood samples. cDNA analyses showed variability in FHIT transcripts, without apparent effects on the predicted amino acid sequence. These different FHIT mRNAs could represent transcripts from an alternative splicing event. Our data indicate that the FHIT mRNA detected in anal cancers and in normal samples is heterogeneous. Immunohistochemical data suggest that the Fhit protein is expressed only in a fraction of the tumor cells, while it is strongly expressed in the epithelial cells of glands of the normal anal mucosa. The absence or poor expression of the Fhit protein in anal cancers suggests a role for this tumor suppressor gene product, as a risk factor, in the onset of this human cancer, as reported before for other human gastrointestinal tumors.