Multiple mutations of the p53 gene in human mammary carcinoma
Multiple mutations of the p53 gene in human mammary carcinoma
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DOI：
10.1016/s0921-8777(99)00053-1
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发表时间：
1999-12-07
期刊：
影响因子：
--
通讯作者：
Nadji, M
中科院分区：
文献类型：
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作者：
Meng, L;Lin, L;Nadji, M
p53抑癌基因的改变是人类肿瘤中最常见的遗传异常。在乳腺癌中，根据疾病的阶段和检测方法，观察到25-60%的突变率。然而，在同一肿瘤中p53基因的多个突变很少报道。在这项研究中，我们探讨了在南佛罗里达乳腺癌患者队列中的p53基因的多重突变的频率。1984年至1986年在迈阿密大学杰克逊医学中心诊断的384例原发性乳腺癌是本研究的对象。对福尔马林固定、石蜡包埋肿瘤的克隆PCR扩增DNA进行p53外显子5至8的序列分析。384例乳腺癌中有234例（61%）有p53突变。其中，36个肿瘤显示一个以上的突变; 31个肿瘤有两个突变，3个显示三个，一个肿瘤有五个突变，一个病例携带六个突变。大多数突变是错义突变（43），其次是沉默突变（35）;大多数发生在单个外显子内。我们的研究表明，乳腺癌中p53抑制基因的多重突变比目前认为的更常见。(C)1999 Elsevier Science B. V.保留所有权利。
Alteration of the p53 tumor suppressor gene is the most common genetic abnormality in human cancer. In breast cancer, depending on the stage of disease and method of detection, mutation rates of 25-60% have been observed. Multiple mutations of p53 gene in the same tumor however, are rarely reported. In this study we explored the frequency of multiple mutations of p53 gene in mammary carcinoma in a cohort of south Florida patients. Three hundred eighty-four cases of primary breast cancer diagnosed between 1984 and 1986 at the University of Miami, Jackson Medical Center were subjects of this study. Sequence analysis of exons 5 through 8 of p53 was performed on cloned PCR-amplified DNA of formalin-fixed, paraffin-embedded tumors. Two hundred thirty-four of 384 breast cancers (61%) had p53 mutation. Of those, 36 tumors showed more than one mutation; 31 tumors had two mutations, three showed three, one tumor had five mutations, and one case carried six mutations. The majority of mutations were missense (43) followed by silent (35); and most occurred within a single exon. Out study suggests that multiple mutations of p53 suppressor gene in breast cancer are more common than currently believed. (C) 1999 Elsevier Science B.V. All rights reserved.