Cheng Liang, MacLennan Gregory T, Zhang Shaobo, Wang Mingsheng, Zhou Ming, Tan Puay-Hoon, Foster Stephanie, Lopez-Beltran Antonio, Montironi Rodolfo
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Clin Cancer Res. 2008 Dec 15;14(24):8087-93. doi: 10.1158/1078-0432.CCR-08-1494.
Renal cell carcinomas are often multifocal. We investigated the genomic signatures of multifocal clear cell renal cell carcinoma to determine whether multiple tumors in the same kidney bear a clonal relationship to one another.
A total of 62 tumors from 26 patients who underwent radical nephrectomy were examined. All patients had multiple separate clear cell renal carcinomas. Loss of heterozygosity analyses were done using five microsatellite polymorphic markers that represent putative tumor suppressor genes on chromosome 3p14 (D3S1300), 7q31 (D7S522), 8p22 (D8S261), 9p21 (D9S171), and 17p13 (TP53). X chromosome inactivation analyses were also done on the renal tumors from the 10 female patients. Chromosome 3p deletion status was determined by dual color interphase fluorescence in situ hybridization analysis in all tumors.
Nineteen of the 26 (73%) patients with multifocal clear cell renal cell carcinoma showed allelic loss in at least 1 of 5 microsatellite loci in separate tumors analyzed. A disconcordant pattern of allelic loss between coexisting kidney tumors was observed in 7 cases. Six cases showed discordant 3p deletion patterns by dual color interphase fluorescence in situ hybridization analysis. Of the eight informative female cases studied by X chromosome inactivation, one showed a discordant nonrandom pattern of X chromosome inactivation. Overall, evidence of independent origin of the multifocal renal tumors was observed in 12 of 26 cases (46%).
Our data suggest that in a significant number of cases of multifocal clear cell renal cell carcinoma, the spatially separate tumors are of different clonal origin and arise independently.
肾细胞癌常为多灶性。我们研究了多灶性透明细胞肾细胞癌的基因组特征，以确定同一肾脏中的多个肿瘤彼此之间是否存在克隆关系。
对26例行根治性肾切除术患者的62个肿瘤进行了检查。所有患者均有多发性独立透明细胞肾癌。使用五个微卫星多态性标记进行杂合性缺失分析，这些标记代表3号染色体p14区域（D3S1300）、7号染色体q31区域（D7S522）、8号染色体p22区域（D8S261）、9号染色体p21区域（D9S171）和17号染色体p13区域（TP53）的假定肿瘤抑制基因。还对10名女性患者的肾肿瘤进行了X染色体失活分析。通过双色间期荧光原位杂交分析确定所有肿瘤的3号染色体p缺失状态。
26例多灶性透明细胞肾细胞癌患者中有19例（73%）在分析的不同肿瘤中至少有1个微卫星位点出现等位基因缺失。7例共存肾肿瘤之间观察到等位基因缺失的不一致模式。6例通过双色间期荧光原位杂交分析显示3p缺失模式不一致。在通过X染色体失活研究的8例信息丰富的女性病例中，1例显示X染色体失活的不一致非随机模式。总体而言，26例中有12例（46%）观察到多灶性肾肿瘤独立起源的证据。
我们的数据表明，在相当数量的多灶性透明细胞肾细胞癌病例中，空间上分离的肿瘤具有不同的克隆起源且独立发生。
