Aberration of oncogenes and tumor suppressor genes in hematopocetic tumors in animals

为了解血液系统恶性肿瘤发生的分子机制，我们对自然发生的淋巴瘤和白血病的癌基因和抑癌基因的异常进行了研究。在核癌基因上，4例猫和1例犬的myc基因发生了突变。在4例猫白血病病例中，2例发现猫白血病病毒(FeLV)转导c-myc基因。对整合区的研究发现，在8例淋巴瘤猫中有一个8kb的共同整合区。由于这个共同的整合区(FIT-1)位于猫科动物的B2染色体上，不同于已知的癌基因和共同的整合区，FIT-1区被认为包括一个新的癌基因。另一方面，我们克隆了猫P53抑癌基因的全长编码序列。该克隆编码386个氨基酸，与人和小鼠p53基因的氨基酸序列同源性分别为82.1%和74.9%。PCR-SSCP(单链构象多态)分析在2例猫淋巴瘤病例中发现异常条带。核苷酸序列测定显示在III和IV保守区有氨基酸替代的点突变。此外，对犬和猫淋巴系统肿瘤T细胞受体和免疫球蛋白基因重排的研究揭示了肿瘤的克隆性、分化阶段及其与癌基因和抑癌基因异常的关系。可以想见，目前的研究为了解血液系统肿瘤的分子发生机制提供了许多有用的发现。

To understand the molecular mechanism of tumorigenesis in hematopoetic malignancies, aberration of oncogenes and tumor suppressor genes were investigated in naturally ocurring lymphomas and leukemias in animals. On the nuclear oncogenes, aberrations of myc gene were observed in 4 feline cases and 1 canine case. In 2 of the 4 feline cases, transduction of c-myc gene by feline leukemia virus (FeLV) was found. Investigation of the integration region revealed a 8-kb common integration region in 8 feline cases with lymphomas. Since this common integration region (fit-1) was located on the feline B2 chromosome and different from known oncogenes and common integration regions, the fit-1 region was considered to include an new oncogene. On the other hand, we cloned a feline p53 tumor suppressor gene cDNA containing its whole coding sequence. This cDNA clone was shown to code 386 amino acids and showed 82.1% and 74.9% amino acid sequence identities with human and mouse p53 genes, respectively. PCR-SSCP (single strand conformation polymorphism) analysis indicated abnormal bands in 2 feline cases of lymphoma. Nucleotide sequence determination revealed point mutations substituting amino acids in the conserved regions of III and IV.Furthermore, a study on the rearrangement of T-cell receptor and immunoglobulin genes in canine and feline lymphoid tumors disclosed the clonality, differentiation stage and their relation with aberrations of oncogenes and tumor suppressor genes. It is conceivable that the present studies have provided many useful findings for understanding the molecular tumorigenesis mechanism of hematopoietic tumors.