Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3.
Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3.
复制标题
结直肠癌中 8p22-p21.3 中推定肿瘤抑制基因的缺失图谱。
作者：
C. Cunningham;M. Dunlop;A. Wyllie;Bird Cc
尽管之前对结直肠肿瘤中获得性杂合性缺失（LOH）的研究表明肿瘤抑制基因可能位于8号染色体的短臂内，但其精确定位仍有待确定。为了获得更准确的位置图，使用八个 8 号染色体多态性标记检查了 120 个结直肠癌，这些标记包括限制性片段长度多态性和基于 (CA)n 重复的微卫星多态性。 91 例提供信息，其中 47 例（51%）检测到 LOH。最常见的标记位于丢失区域，映射到染色体 8p22 的脂蛋白脂肪酶基因 (LPL)。根据对显示 8p 内断点的肿瘤的研究，建立了从 LPL 向着丝粒延伸至锚蛋白 1 基因 (ANK1) 的常见缺失区域，该区域被映射到 8p21.1-11.2。这与其他结直肠肿瘤 (8p23.1-p21.3) 和膀胱肿瘤 (8p21-q11.2) 研究中观察到的常见缺失区域重叠。总而言之，结直肠癌的结果描绘了 8p22-p21.3 中的一个区域，假定的肿瘤抑制基因必定位于该区域。在同一肿瘤中，染色体 8p 缺失似乎与涉及 5q 和 17p 的缺失无关。未发现 8p 缺失的存在与肿瘤部位或阶段、或诊断时患者的性别或年龄之间存在关系。
Although previous studies of acquired loss of heterozygosity (LOH) in colorectal tumours have suggested that a tumour suppressor gene may lie within the short arm of chromosome 8, its precise localisation remains to be determined. To obtain a more accurate positional map 120 colorectal cancers were examined with eight chromosome 8 polymorphic markers comprising both restriction fragment length polymorphisms and microsatellite polymorphisms based on (CA)n repeats. 91 cases were informative and LOH was detected in 47 (51%). The markers most commonly sited within the lost region mapped to the lipoprotein lipase gene (LPL) at chromosome 8p22. From study of tumours showing break-points within 8p, a common region of deletion was established extending centromerically from LPL to the ankyrin 1 gene (ANK1) which is mapped to 8p21.1-11.2. This overlaps with common deleted regions observed in other studies of colorectal tumours (8p23.1-p21.3) and bladder tumours (8p21-q11.2). Taken together, the results in colorectal cancer delineate a region in 8p22-p21.3 where the putative tumour suppressor gene must lie. The chromosome 8p deletions appear to be independent of those involving 5q and 17p in the same tumours. No relationship was found between the presence of 8p deletion and site or stage of the tumour, or the sex or age of the patient at diagnosis.