Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog
Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog
复制标题
犬淋巴瘤中 p53 基因的突变以及狗种系 p53 突变的证据
作者：
N. Veldhoen;J. Stewart;Robert Brown;J. Milner
p53基因的突变与犬的许多非淋巴癌相关。本研究调查了犬原发性和继发性淋巴瘤患者的p53基因状态。8例患者中有3例出现p53基因突变。其中包括1例生殖系突变患者和2例继发性淋巴瘤相关的p53新发突变患者。在三名犬患者的原发性和继发性肿瘤中也观察到p53基因的等位基因丢失。结果表明，狗中存在种系p53突变，并且可能与某些品种已知的癌症易感性有关。治疗相关的p53点突变的存在被认为是与化疗耐药的继发性淋巴瘤。DNA损伤性化疗在p53基因的从头突变的病因作用进行了讨论。犬肿瘤发生中p53失活的特征可能为评估抗癌药物的疗效和最佳治疗方案提供有价值的临床模型。
Mutations of the p53 gene are associated with a number of non-lymphoid cancers of the dog. The present study investigates the p53 gene status within canine patients treated for primary and secondary lymphoma. Three out of eight patients exhibited p53 gene mutations. These included one patient with a germ line mutation and two patients with de novo p53 mutations associated with the secondary lymphoma. Allelic loss of the p53 gene was also observed within primary and secondary tumours of the three canine patients. The results indicate that germ line p53 mutations exist in dogs and may be involved in the known predisposition of some breeds to cancer. The presence of therapy-related p53 point mutations was found to be associated with chemoresistant secondary lymphomas. A causative role for DNA-damaging chemotherapy in de novo mutation of the p53 gene is discussed. Characterization of p53 inactivation in canine tumorigenesis may provide a valuable clinical model for assessing the efficacy and optimal therapeutic regimens of anti-cancer agents.