Structure and expression of the human FHIT gene in normal and tumor cells

The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these gene...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-02, Vol.57 (3), p.504-512
Main Authors: DRUCK, T, HADACZEK, P, ROTHSTEIN, J, MCCUE, P, COTTICELLI, M. G, INOUE, H, CROCE, C. M, HUEBNER, K, FU, T.-B, OHTA, M, SIPRASHVILI, Z, BAFFA, R, NEGRINI, M, KASTURY, K, VERONESE, M. L, ROSEN, D
Format: Article
Language:English
Subjects:
Acid Anhydride Hydrolases
Base Sequence
Biological and medical sciences
Blotting, Southern
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Exons
Fundamental and applied biological sciences. Psychology
Gene Deletion
Gene Expression
Humans
Molecular and cellular biology
Molecular Sequence Data
Neoplasm Proteins
Neoplasms - genetics
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Proteins - analysis
Proteins - genetics
Tumor Cells, Cultured
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Summary:The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein.
ISSN:0008-5472
1538-7445