Construction of a Cosmid Contig Surrounding the Region of the Fragile Histidine Triad Gene (FHIT)
Paisley, Christa Marie
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Cancer is a genetic disease that is characterized as unregulated growth of cells leading to a malignant neoplasm. The neoplasm, tumor, has the potential to manifest invasiveness and metastasize to other organs of the body through the circulatory system. Chromosome 3 represents one of the most intensely studied chromosomes with respect to cancer development. One of the target regions, 3p14.2, contains the FRA3B inducible fragile site, a hereditary renal cell carcinoma associated translocation, t(3;8), and a candidate tumor suppressor gene, Fragile Histidine Triad (FHIT) gene. The FHIT gene (1 kb) consists of ten exons (5-9 are coding exons) distributed over more than 500 kb, of which spans the FRA3B fragile site. Aberrant transcripts of FHIT observed in many cancers (colon, esophagus, stomach and lung) have suggested the FHIT gene as a candidate tumor suppressor gene, yet evidence exists to contradict this notion as well. Therefore, I constructed a partial cosmid contig using FHIT exon oligonucleotide primers (exons 6 through 10) and a Yeast Artificial Chromosome (YC750F1) from the Jean Dausset-CEPH (CEPH) Yeast Artificial Chromosome (YAC) library (a library constructed under the efforts of the Human Genome Project for mapping the human genome). The intent of this project was three fold. One purpose of the partial cosmid contig construction was to provide a tool for studying the FHIT gene more closely and its potential role as a tumor suppressor gene. The cosmid contig will also be valuable in researching the intron sequences between the FHIT exons for other possible tumor suppressor genes. Finally, the cosmid contig will be useful in future studies on the instability of the FRA3B common fragile site and its role in cancer breakpoint development.