Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages. In contrast to tumor stage, different tumor grades are associated with distinct gene expression signatures. Furthermore, a subset of genes associated with high tumor grade is quantitatively correlated with the transition from preinvasive to invasive growth.

Snow pool Aedes mosquitoes are identified easily and accurately by microscopic examination of 4th instars or male genitalia. Early instars and females cannot be identified accurately. We demonstrate that restriction fragment-length polymorphisms (RFLP) in the internal transcribed spacer (ITS) of the nuclear ribosomal DNA cistron are specific to each of 13 snow pool Aedes species found in northern Colorado. The ITS was amplified by the polymerase chain reaction (PCR) and digested with AluI and MspI restriction endonucleases. Differences in the sizes of digested fragments among the 13 species were so slight that they could only be resolved with polyacrylamide gel electrophoresis and visualized with silver staining. A key to species found in the Rocky Mountains of northern Colorado was constructed using the PCR-RFLP patterns. Three of the species were collected in California and had identical PCR-RFLP patterns, indicating that restriction sites in the ITS may be conserved within some species.

TP53 is involved in the regulation of the cell cycle, response to DNA damage and induction of apoptosis. Mutations in this gene are thought to contribute to the development, progression or both of a variety of tumors, including human malignant glioma. Molecular analyses of primary malignant gliomas have demonstrated cellular heterogeneity in gene loss, rearrangement, amplification, transcription and translation. Furthermore, the rapid recurrence of this tumor demonstrates the presence of cells that are intrinsically resistant to therapy. Whether mutations in TP53 contribute to therapy resistance and tumor recurrence in malignant gliomas is not known. To determine if TP53 mutations are indicative of cells with a selective advantage that contributes to the survival and/or recurrence of glial tumors, we undertook a study to compare matched cells from primary and recurrent tumors from the same patients. We will present results from our analysis of TP53 mutations present in cells derived from both primary and recurrent glial tumors using polymerase chain reaction and sequence analysis to screen for mutations in exons 5-8 of TP53.