Aberrations of the p53 tumor suppressor gene in various tumors in dogs
Aberrations of the p53 tumor suppressor gene in various tumors in dogs
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DOI：
10.2460/ajvr.2001.62.433
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发表时间：
2001-03-01
影响因子：
1
通讯作者：
Tsujimoto, H
中科院分区：
文献类型：
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作者：
Setoguchi, A;Sakai, T;Tsujimoto, H
目的-评估犬自然发育肿瘤中p53抑癌基因的畸变。样本群体-来自15只患有各种肿瘤的犬的肿瘤标本，包括恶性淋巴瘤（7只犬）、单核细胞白血病（1）、乳腺腺瘤（1）、乳腺良性混合瘤（1）、横纹肌肉瘤（1）、结肠癌（1）和骨肉瘤(3).程序-通过逆转录酶-聚合酶链反应和单链构象多态性分析检测这些肿瘤组织中p53基因的畸变，使用覆盖犬p53基因整个开放阅读框的3个片段，然后对异常条带进行核苷酸测序。结果-在15个肿瘤标本中的7个中检测到导致野生型p53的多个氨基酸取代的点突变、缺失和插入。患有恶性淋巴瘤、单核细胞白血病、横纹肌肉瘤、结肠癌和骨肉瘤的狗。在这 7 只狗中，有 2 只狗的两个等位基因上都有 p53 基因畸变，而 5 只狗的 1 个等位基因上有 p53 基因畸变，同时缺乏野生型 p53 转录本。在这些肿瘤中检测到的 p53 基因的许多畸变位于反式激活、DNA 结合和寡聚化结构域。结论和临床相关性——狗体内各种自然发育的肿瘤通常具有 p53 肿瘤抑制基因失活，这可能是肿瘤发生过程中多个逐步遗传变化之一。这项研究表明p53基因可以成为犬肿瘤基因治疗的靶点。
Objective-To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs.Sample Population-Tumor specimens from 15 dogs with various tumors, including malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adenoma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon cancer (1), and osteosarcoma (3).Procedure-Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase-polymerase chain reaction and single-strand conformation polymorphism analysis, using 3 fragments that covered the entire open reading frame of the canine p53 gene, followed by nucleotide sequencing of the abnormal bands.Results-Point mutations, deletions, and insertions resulting in a number of amino acid substitutions of wild-type p53 were detected in 7 of the 15 tumor specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdomyosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberrations of the p53 gene on both alleles, whereas 5 had aberrations of the p53 gene on 1 allele and concurrently lacked the wild-type p53 transcript. Many of the aberrations of the p53 gene detected in these tumors were located in the transactivation, DNA binding, and oligomerization domains.Conclusions and Clinical Relevance-Various naturally developing tumors in dogs often have inactivation of the p53 tumor suppressor gene, which may be 1 of the multiple step-wise genetic changes during tumorigenesis. This study indicates that p53 gene can be a target for gene therapy for tumors in dogs.