Analysis of disease genes in salivary gland tumor

我们已经鉴定出小鼠INT-3基因的人类同源基因INT3，位于人类主要组织相容性复合体(MHC)的II类和III类区域的交界处，该区域是唾液腺肿瘤染色体异常的邻近区域，并怀疑该INT3基因是导致唾液腺肿瘤发生的危险基因。分离并测序INT3c DNA克隆。对INT3基因克隆的核苷酸序列分析表明，该基因由Notch同源基因的胞内部分和跨膜区的胞外部分、Notch/Lin-12重复序列和EGF样重复序列组成。在INT3基因5‘-上游区域，(CTG)n重复序列表现为微卫星多态性，不同单倍型的重复数不同。在66个人类白细胞抗原纯合子B淋巴母细胞系中发现了5个等位基因。为探讨(CTG)n重复序列多态性是否与涎腺肿瘤相关，对19例涎腺肿瘤标本进行了(CTG)n重复序列多态性分析。在日本人群中也发现了四个等位基因。在这个肿瘤中没有发现这种重复序列的扩展或新的等位基因。在这个肿瘤中，以INT3cDNA插入为探针进行基因组Southern杂交分析，也没有检测到大规模的缺失或易位。

We have identified a human homologue of the mouse int-3 gene, INT3 located on the junction of the class II abd class III regions of the human major histocompatibility complex (MHC) , the neighboring region of a chromosome aberration in salivary gland tumor and suspected that this INT3 gene is acandidate gene responsible for the development of salivary gland tumor. INT3 cDNA clones were isolated and sequenced. Analyzes of the nucleotide sequences of the INT3 cDNA clones suggested that the INT3 gene was composed of the intracelluar portion of Notch-homologous genes and the extracellular portion of the transmembrane region, Notch/lin-12 repeats, and EGF-like repeats. In the the 5'-upstream region of the INT3 gene, (CTG) n repeats showed microsatellite polymorphism with various numbers of repeats for different HLA haplotypes. Five alleles have been identified in 66 HLA homozygous B-lymphoblastoid cell lines. To ascertain if (CTG) n repeats polymorphism may correlate with salivary gland tumor, polymorphism of the (CTG) n repeats have been analyzed in 19 samples of salivary gland tumor. Four alleles have been identified as well as in a Japanese population. No expansion or new alleles of this repeats were found in this neoplasia. In this neoplasia, no large-scale deletion or translocation, either was detected using genomic Southern hybridization analysis by the INT3 cDNA insert as a probe.