Hughson M D, Dickman K, Bigler S A, Meloni A M, Sandberg A A
Department of Pathology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Cancer Genet Cytogenet. 1998 Oct 15;106(2):93-104. doi: 10.1016/s0165-4608(98)00068-5.
Clear-cell and papillary renal cell carcinomas (RCCs) have specific genetic changes that allow them to be classified on the basis of histopathology and on the basis of cytogenetic and molecular genetic findings. Clear-cell carcinomas are characterized by a deletion of gene sequences on the short arm of chromosome 3 (3p). Papillary RCCs do not have 3p deletions but have an increase in chromosomal number that usually includes trisomies of chromosomes 7 and 17. This study was undertaken to determine whether PCR-amplified DNA microsatellites can be used to detect numerical abnormalities of chromosomes 7 and 17 and whether the numerical abnormalities and 3p deletions that are detected by microsatellite analysis can be correlated with histopathologic tumor types. A series of histologically unambiguous RCCs consisting of three papillary and ten clear-cell RCCs were studied by cytogenetics and by fluorescence in situ hybridization (FISH) with chromosome 7 and 17 centromeric probes. Microsatellites on the long and short arms of chromosomes 3, 7, and 17 were amplified in paired normal tissue and tumor samples, and the reaction products were analyzed for differences between the normal and the tumor allele ratios. Clear-cell carcinomas showed loss of heterozygosity (LOH) of 3p but not 3q alleles in eight of ten cases. LOH of 3p and 3q was seen in one case of papillary RCC that cytogenetically had two normal chromosomes 3. This indicated a nondisjunction duplication that could be confused with monosomy 3 if only microsatellite studies were performed. Differences in microsatellite allele ratios between normal tissue and tumor correlated with the presence of trisomy 7 that was identified in clear-cell and papillary RCCs by cytogenetics and by FISH. Microsatellite analysis did not detect numerical chromosome 17 abnormalities in the papillary RCCs but did show an abnormality in one clear-cell carcinoma that was markedly aneusomic for chromosomes 7 and 17 by FISH. In this collection of cases, microsatellite amplification genetically distinguished only clear-cell RCCs showing 3p but not 3q LOH as a separate class of tumors. The method detected abnormalities in chromosome number that were found in both clear-cell and papillary RCCs.
透明细胞型和乳头状肾细胞癌（RCC）具有特定的基因改变，这使得它们能够基于组织病理学以及细胞遗传学和分子遗传学发现进行分类。透明细胞癌的特征是3号染色体短臂上的基因序列缺失（3p）。乳头状RCC没有3p缺失，但染色体数目增加，通常包括7号和17号染色体三体。本研究旨在确定聚合酶链反应（PCR）扩增的DNA微卫星是否可用于检测7号和17号染色体的数目异常，以及微卫星分析检测到的数目异常和3p缺失是否与组织病理学肿瘤类型相关。通过细胞遗传学以及使用7号和17号染色体着丝粒探针的荧光原位杂交（FISH），对一系列组织学明确的RCC进行了研究，其中包括3例乳头状RCC和10例透明细胞型RCC。对3号、7号和17号染色体长臂和短臂上的微卫星在配对的正常组织和肿瘤样本中进行扩增，并分析反应产物中正常和肿瘤等位基因比例的差异。在10例透明细胞癌中，有8例显示3p等位基因杂合性缺失（LOH），但3q等位基因未缺失。在1例乳头状RCC中观察到3p和3q的LOH，该病例细胞遗传学显示有两条正常的3号染色体。这表明存在不分离复制，如果仅进行微卫星研究，可能会与3号染色体单体混淆。正常组织和肿瘤之间微卫星等位基因比例的差异与7号染色体三体的存在相关，这是通过细胞遗传学和FISH在透明细胞型和乳头状RCC中确定的。微卫星分析未检测到乳头状RCC中17号染色体的数目异常，但在1例透明细胞癌中显示出异常，该病例通过FISH显示7号和17号染色体明显非整倍体。在这组病例中，微卫星扩增仅从基因上区分出显示3p而非3q LOH的透明细胞型RCC作为一类单独的肿瘤。该方法检测到了在透明细胞型和乳头状RCC中均存在的染色体数目异常。
