Sugimura J, Tamura G, Suzuki Y, Fujioka T
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Pathol Int. 1997 Feb-Mar;47(2-3):79-83. doi: 10.1111/j.1440-1827.1997.tb03724.x.
Loss-of-heterozygosity (LOH) has been studied on 3p (von Hippel-Lindau gene locus), 5q and 17p (p53 gene locus) by a polymerase chain reaction (PCR)-based strategy in 42 sporadic renal cell carcinomas (RCC). LOH at seven microsatellite loci on 5q was investigated because a tumor suppressor gene on 5q involved in the development and/or progression of RCC has not yet been identified. LOH was found in seven (17%) RCC at single or multiple loci on 5q, 38% (11/29 informative cases) on 3p, and 6% (2/35 informative cases) on 17p. Replication error (RER) was present in 10% (4/42) RCC at single or multiple loci. The minimum region of deletion on 5q to account for LOH was mapped to 5q31.1 (interferon regulatory factor-1; IRF-1 locus), where LOH was detected in 23% (6/26 informative cases). LOH on 3p and 5q occurred in both stage 2 and more advanced (stage 3 and 4) tumors at similar incidences (41 and 33% on 3p; and 24 and 22% on 5q, respectively), suggesting that LOH on these chromosomes is an early genetic event. All RCC exhibiting LOH on 3p or 5q (IRF-1 locus) were the clear cell or the mixed clear and granular cell types. These findings suggest that LOH on 3p and 5q plays an important role in the genesis of clear cell RCC. In addition, only one tumor exhibited LOH on both 3p and 5q, which suggests that LOH occurs not sequentially but independently.
采用基于聚合酶链反应（PCR）的方法，对42例散发性肾细胞癌（RCC）的3p（冯希佩尔-林道基因位点）、5q和17p（p53基因位点）进行杂合性缺失（LOH）研究。对5q上7个微卫星位点的LOH进行了研究，因为5q上一个参与RCC发生和/或进展的肿瘤抑制基因尚未被鉴定。在5q的单个或多个位点上，7例（17%）RCC中发现了LOH，3p上为38%（11/29例信息性病例），17p上为6%（2/35例信息性病例）。10%（4/42）的RCC在单个或多个位点存在复制错误（RER）。5q上导致LOH的最小缺失区域定位于5q31.1（干扰素调节因子-1；IRF-1位点），在23%（6/26例信息性病例）中检测到LOH。3p和5q上的LOH在2期及更晚期（3期和4期）肿瘤中的发生率相似（3p上分别为41%和33%；5q上分别为24%和22%），这表明这些染色体上的LOH是早期遗传事件。所有在3p或5q（IRF-1位点）表现出LOH的RCC均为透明细胞型或透明细胞与颗粒细胞混合型。这些发现表明，3p和5q上的LOH在透明细胞RCC的发生中起重要作用。此外，只有1例肿瘤在3p和5q上均表现出LOH，这表明LOH并非顺序发生而是独立发生的。
