Positive correlation between allelic loss at chromosome 14q24-31 and poor prognosis of patients with renal cell carcinoma
Positive correlation between allelic loss at chromosome 14q24-31 and poor prognosis of patients with renal cell carcinoma
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DOI：
10.1016/j.urology.2004.03.015
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发表时间：
2004-07-01
期刊：
影响因子：
2.1
通讯作者：
Shimizu, K
中科院分区：
文献类型：
--
作者：
Kaku, H;Ito, S;Shimizu, K
目标.报道我们开发的一种新的应用间AN长聚合酶链反应（PCR）的基因组扫描，以筛选肿瘤特异性改变的肿瘤DNA。利用这种方法，我们检测到一个重排的染色体区域在肾细胞癌（RCC）。然后，我们使用微卫星标记检查了该区域的肿瘤特异性等位基因丢失，并确定该等位基因丢失与患者的临床病理特征之间是否存在关系。使用RCC DNA样品和对人类重复序列Alu的次要子集特异的引物进行Alu间长PCR基因组扫描方法。我们用7个微卫星标记分析了42对配对的正常和非乳头状肾细胞癌组织的DNA样本。间Alu长PCR基因组扫描方法揭示了染色体14 q24 -31上的改变的DNA区域，这是几个推定的肿瘤抑制基因的位置。42例肾癌中23例（54.8%）在染色体14 q24 -31上的7个微卫星标记中至少有1个杂合性缺失。普遍的损失区域被限制在D14 S67周围的2-Mb区域。14 q24 -31杂合性缺失与肿瘤分期呈正相关（P < 0.05）。我们还发现14 q24 -31等位基因丢失的病例预后不良（P = 0.045）。我们的inter-Alu长PCR基因组扫描方法是一种强有力的方法，用于筛选DNA改变，我们的数据表明，染色体14 q24 -31区域包含可能的肿瘤抑制基因与RCC的进展。(C)2004年爱思唯尔公司
Objectives. To report our development of a new application of the inter-AN long polymerase chain reaction (PCR) for genomic scanning to screen for tumor-specific alterations in tumor DNA. Using this method, we detected a rearranged chromosomal region in renal cell carcinomas (RCCs). We then examined tumor-specific allelic loss in this region using microsatellite markers and determined whether a relationship was present between this allelic loss and the clinicopathologic features of the patients.Methods. The inter-Alu long PCR genomic scan method was performed using RCC DNA samples and primers specific for a minor subset of the human repeat sequence Alu. We analyzed DNA samples from 42 pairs of matched normal and nonpapillary RCC tissues with seven microsatellite markers.Results. The inter-Alu long PCR genomic scan method revealed an altered DNA region on chromosome 14q24-31, which is the location of several putative tumor suppressor genes. At least one of seven microsatellite markers on chromosome 14q24-31 showed loss of heterozygosity in 23 (54.8%) of 42 informative cases of RCC. The prevalent loss region was confined to a 2-Mb region around D14S67. We found a positive correlation between the presence of the loss of heterozygosity on 14q24-31 and tumor stage (P < 0.05). We also found that cases with allelic loss at 14q24-31 had a poor prognosis (P = 0.045).Conclusions. Our inter-Alu long PCR genomic scan method is a powerful method for the screening of DNA alterations, and our data suggest that the chromosome 14q24-31 region contains likely tumor suppressor genes associated with the progression of RCC. (C) 2004 Elsevier Inc.