Kenck C, Bugert P, Wilhelm M, Kovacs G
Department of Urology, Ruprecht-Karls-University of Heidelberg, Germany.
Oncogene. 1997 Mar 6;14(9):1093-8. doi: 10.1038/sj.onc.1200915.
Previous karyotyping showed an unbalanced translocation between chromosome 3p11.2-p13 and chromosome 5q22 leading to duplication of chromosome 5q22-qter region in nonpapillary renal cell carcinomas. In order to determine the breakpoint at chromosome 5q22 at the molecular level, we have investigated 50 sporadic nonpapillary renal cell carcinomas from consecutive nephrectomies and 24 renal cell carcinomas obtained from two patients with von Hippel-Lindau disease. We used seven DNA markers mapped to and around the APC and MCC genes to detect allelic imbalance. We observed a duplication of chromosome 5q sequences in 11 of 23 informative sporadic tumours and in 18 of 24 hereditary tumours. We determined a breakpoint cluster between the APC and MCC genes at chromosome 5q22. In addition we have found a partial duplication of the smallest overlapping region of about 1.5 Mb sequences including the MCC gene in seven tumours without visible alteration of chromosome 5q in the karyotype. We suggest that this DNA segment harbours a gene or gene cluster, the altered dosage of which is important for the growth of nonpapillary renal cell carcinomas.
先前的核型分析显示，在非乳头状肾细胞癌中，3号染色体短臂1区1带2亚带至1区3亚带与5号染色体长臂2区2带之间存在不平衡易位，导致5号染色体长臂2区2带至末端区域重复。为了在分子水平上确定5号染色体长臂2区2带的断点，我们研究了50例连续肾切除术中获得的散发性非乳头状肾细胞癌，以及2例冯·希佩尔-林道病患者的24例肾细胞癌。我们使用了7个定位在腺瘤性息肉病（APC）基因和微卫星结肠癌（MCC）基因及其周围的DNA标记来检测等位基因失衡。我们在23例有信息的散发性肿瘤中的11例以及24例遗传性肿瘤中的18例中观察到5号染色体长臂序列重复。我们确定了5号染色体长臂2区2带中APC基因和MCC基因之间的一个断点簇。此外，我们在7例核型中5号染色体长臂无可见改变的肿瘤中发现了约1.5兆碱基序列的最小重叠区域的部分重复，其中包括MCC基因。我们认为，该DNA片段包含一个基因或基因簇，其剂量改变对非乳头状肾细胞癌的生长很重要。
