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

为了了解造血系统恶性肿瘤发生的分子机制，研究了动物自然发生的淋巴瘤和白血病中癌基因和抑癌基因的畸变。在核癌基因上，4例猫和1例犬的myc基因出现了畸变。在4例猫病例中，2例发现c-myc基因被猫白血病病毒（FeLV）转导。对8例淋巴瘤猫的整合区进行了调查，发现了一个8 kb的共同整合区。由于这个共同整合区（fit-1）位于猫的B2染色体上，不同于已知的癌基因和共同整合区，因此fit-1区域被认为包含一个新的癌基因。另一方面，我们克隆了一个包含完整编码序列的猫p53肿瘤抑制基因cDNA。该cDNA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（单链构象多态性）分析在2例猫淋巴瘤中发现异常条带。此外，通过对犬、猫淋巴样肿瘤中t细胞受体和免疫球蛋白基因重排的研究，揭示了它们的克隆性、分化阶段及其与癌基因和抑癌基因畸变的关系。可以想象，本研究为理解造血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.