Project: Research project

Project Details


We have developed a highly sophisticated computerized scanning system which
permits the quantitation of expression of each of many thousands of cloned
sequences in colonic biopsy specimens. We have used this system with
biopsy samples of flat mucosa, premalignant adenoma, and carcinoma, from
well defined populations which vary in their risk (both genetic and
dietary) for, and pattern of development of, colon cancer. Thus, we have
begun to develop a large computerized data base on expresison of each of
4000 sequences from an HT-29 human colon carcinoma cDNA library, and a
number of the proto-onc genes, in human tissue during the progression to
colon cancer. From these data, we have identified a number of sequences
which may characterize various stages in the progression of the disease,
and molecular analysis, including nucleotide sequencing of some of these,
has begun.

We propose to use biopsy material from our extensive and well defined
patient population together with this method of analysis to further define
the changes of gene expression which characterize premalignant alterations,
including an expansion of the proliferative compartment which we have
documented in the flat mucosa of high risk individuals. In addition, the
heterogenity of gene expression in tumors will be studied to identify
markers which distinguish early form late adenomas, and others which may be
indicative of invasive or metastatic potential. Utilizing methodology
related to that we have reported, the cell type, number and location of
cells within the colonic crypt or tumor which express these sequences will
be analyzed by in situ hybridization of labeled probes to frozen, fixed
sections of biopsy tissue taken at various stages from patients at
differing risk for development of colon cancer. Finally, the molecular
analysis of sequences identified in these experiments will be continued.
Effective start/end date12/31/8912/31/89


  • Genetics
  • Molecular Biology
  • Cancer Research
  • Oncology


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