摘要:
Polyclonal and monoclonal antibodies which recognize mutant epidermal growth factor receptors (EGFR) have been produced. The EGFR gene is amplified in 40% of malignant gliomas and frequently the amplified genes are rearranged. Internal deletions in four glioma cell lines created an epitope which was not present in normal EGFR. These mutant were characterized as expressing mutant type 1I EGFR and were found in a small percent of gliomas. Antibodies against these epitopes are useful for diagnosis of specific gliomas which express mutant type 1I EGFR.
摘要:
The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Furthermore, these studies document the existence of tumor specific cell molecules resulting from somatic mutation.
摘要:
The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Furthermore, these studies document the existence of tumor specific cell molecules resulting from somatic mutation.
摘要:
Deletions in the EGF-R gene are found in many gliomas, breast tumors, and lung tumors. A particular truncated EGFR protein has been found in many tumors and provides diagnostic and therapeutic modalities.
摘要:
Deletions in the EGF-R gene are found in many gliomas, breast tumors, and lung tumors. A particular truncated EGFR protein has been found in many tumors and provides diagnostic and therapeutic modalities.
摘要:
The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Furthermore, these studies document the existence of tumor specific cell molecules resulting from somatic mutation.
摘要:
Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.
摘要:
Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.
摘要:
Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
摘要:
To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.