Assuntos
Proteínas de Transporte/genética , Desmina/genética , Ligação Genética , Proteínas dos Microfilamentos/genética , Animais , Galinhas , Mapeamento Cromossômico , Cromossomos Humanos Par 2 , DNA Complementar , Deleção de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Ratos , TensinasRESUMO
SAS is a recently identified member of the transmembrane 4 superfamily (TM4SF) that is frequently amplified in human sarcomas. To further its characterization and to confirm its classification, the genomic structure of the SAS gene was determined. The SAS gene covers approximately 3.2 kb of DNA. It contains six exons within its translated region, three of which are highly conserved in the TM4SF. 5' to the translation start site are two putative transcription start sites, two CCAAT consensus sequences, and potential binding sites for both Sp1 and ATF transcription factors. Comparison of SAS organization to human ME491, CD9, and CD53 and murine CD53 and TAPA-1 confirms that SAS is a member of this family of genes and is consistent with the theory that these genes arose through duplication and divergent evolution.
Assuntos
Genes , Glicoproteínas de Membrana , Proteínas de Membrana/genética , Família Multigênica , Proteínas de Neoplasias/genética , Sarcoma/genética , Sequência de Aminoácidos , Animais , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T/genética , Sequência de Bases , Sequência Consenso , DNA/genética , Éxons/genética , Amplificação de Genes , Humanos , Íntrons/genética , Camundongos/genética , Dados de Sequência Molecular , Filogenia , Glicoproteínas da Membrana de Plaquetas/genética , Sequências Reguladoras de Ácido Nucleico , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Tetraspanina 25 , Tetraspanina 28 , Tetraspanina 29 , Tetraspanina 30 , TetraspaninasRESUMO
Amplification of 12q13-14 occurs in a subset of human sarcomas including malignant fibrous histiocytoma and liposarcoma. This chromosomal region has previously been found to include a number of growth-related genes including the GLI proto-oncogene and the p53-associated protein, MDM2. We now report the characterization of SAS (sarcoma amplified sequence), a novel transcript found in this region. Sequence analysis demonstrates that SAS is a novel member of a transmembrane protein family (transmembrane 4 superfamily or TM4SF) thought to be involved in growth-related cellular processes. This observation adds a TM4SF protein to the cluster of genes at 12q13-14 frequently amplified in human sarcomas.
Assuntos
Amplificação de Genes , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Sarcoma/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Células Cultivadas , Cromossomos Humanos Par 12 , Sequência Consenso , Humanos , Dados de Sequência Molecular , Proto-Oncogene Mas , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , TetraspaninasRESUMO
Cytogenetic analysis of liposarcomas has demonstrated that translocation (12;16) (q13.3;p11.2) is characteristic of the myxoid subtype of this adipose tissue tumor. Our previous results suggested that the GLI gene is close to the translocation breakpoint on chromosome 12. We now describe a yeast artificial chromosome (YAC) that contains GLI and spans the chromosome 12 region involved in the t(12;16) breakpoint. This clone will permit rapid definition of the genetic region surrounding the breakpoint and allow isolation of the gene presumably affected by the translocation.
Assuntos
Cromossomos Fúngicos , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 16 , Biblioteca Gênica , Lipossarcoma/genética , Translocação Genética , Clonagem Molecular , Genoma Humano , HumanosRESUMO
Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated SAS (sarcoma amplified sequence). In the present study, a series of soft tissue sarcomas was studied to characterize further the phenomenon of SAS amplification. Seven of 22 (32%) malignant fibrous histiocytomas and three liposarcomas contained SAS amplification. Strikingly, all of the tumors with SAS amplification occurred in central sites (i.e., in the abdominal or inguinal regions) rather than in the extremities (i.e., in the arms of legs). These observations demonstrate that SAS amplification occurs with a significant frequency in mesenchymal tumors and is particularly associated with abdominal disease.
Assuntos
Amplificação de Genes , Histiocitoma Fibroso Benigno/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Amplification of cellular oncogenes occurs frequently in several human cancers and is an important mechanism of increased gene expression. Identification of amplified genes in tumor cells has proved to be a useful approach for understanding genetic alterations in cancer. Previous procedures for isolating probes from amplified DNA sequences have relied on tissue culture cells, limiting the range of tumors that can be studied and raising questions of in vitro artifact. We have circumvented these problems by combining in gel renaturation of amplified sequences with the polymerase chain reaction. Using this approach, we have identified and partially cloned a DNA amplification unit from biopsies of human malignant fibrous histiocytoma. This amplification unit is derived from chromosome 12q13-14, a site commonly involved in rearrangements in soft tissue tumors, and contains at least one transcribed region (designated SAS, for sarcoma amplified sequence).
