title: Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2.
abstract: Cancer-associated chromosomal aberrations often involve regions containing fragile sites. FRA7G is a common aphidicolin-inducible fragile site at 7q31.2, showing loss of heterozygosity in human malignancies. To investigate the structure of FRA7G, we constructed a bacterial artificial chromosome contig spanning the region between marker D7S486 and Met H. Analysis of the FRA7G sequence allowed us to identify a gene encoding a 421-amino-acid protein with three LIM domains and 89% identity to murine Testin. We determined the genomic structure of the human TESTIN locus and characterized three alternative transcripts. Although TESTIN mRNA is expressed in all normal human tissues examined, we observed lack of expression in 22% of cancer cell lines and 44% of the cell lines derived from hematological malignancies. We further determined that in most of these cases the inactivation of TESTIN expression is due to methylation of a CpG island. Analysis of the TESTIN coding region in 26 tumor cell lines revealed three missense mutations. Our findings suggest that TESTIN may represent a candidate tumor suppressor gene at 7q31.2.
authors.affiliation: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: C
authors.initials: C
authors.lastname: Tatarelli
authors.forename: A
authors.initials: A
authors.lastname: Linnenbach
authors.forename: K
authors.initials: K
authors.lastname: Mimori
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000235:genetics; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D007438:Introns; D060588:LIM Domain Proteins; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020161:Physical Chromosome Mapping; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C429688:TES protein, human; D025521:Tumor Suppressor Proteins; D004247:DNA