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不同人体实体瘤中1号染色体短臂杂合性缺失:与生存的关联

Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival.

作者信息

Ragnarsson G, Eiriksdottir G, Johannsdottir J T, Jonasson J G, Egilsson V, Ingvarsson S

机构信息

Department of Pathology, University and National Hospital of Iceland, Reykjavik.

出版信息

Br J Cancer. 1999 Mar;79(9-10):1468-74. doi: 10.1038/sj.bjc.6690234.

Abstract

The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30-64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35-p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis.

摘要

利用15个多态性微卫星标记,对683例不同部位的人类实体瘤的1号染色体短臂远端进行了分析。在369例(占肿瘤的54%)中至少在一个位点观察到杂合性缺失(LOH)。根据肿瘤部位的不同,检测到的LOH范围为30%-64%。不同肿瘤部位LOH的主要结果如下:胃,20/38(53%);结肠和直肠,60/109(55%);肺,38/63(60%);乳腺,145/238(61%);子宫内膜,18/25(72%);卵巢,17/31(55%);睾丸,11/30(37%);肾,22/73(30%);甲状腺,4/14(29%);肉瘤,9/14(64%)。在1p36.3、1p36.1、1p35-p34.3、1p32和1p31区域观察到高比例的LOH,提示存在肿瘤抑制基因。1号染色体短臂上的所有这些区域在不止一种肿瘤类型中显示出高LOH。然而,在不同肿瘤部位检测到了不同的LOH模式。在乳腺癌患者中,1号染色体有无LOH的生存曲线有显著差异。多变量分析表明,乳腺肿瘤中1p的LOH比我们模型中测试的其他变量(包括淋巴结转移)更能作为预后指标。

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