Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma.
Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma.
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DOI：
10.1038/bjc.1993.101
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发表时间：
1993-03
影响因子：
8.8
通讯作者：
Trowsdale, J
中科院分区：
文献类型：
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作者：
Foulkes, W D;Ragoussis, J;Stamp, G W;Allan, G J;Trowsdale, J
通过杂合性丢失（洛）研究肿瘤中的遗传变化是鉴定可能含有肿瘤抑制基因的染色体区域的有力技术。利用限制性片段长度多态性分析，用少量探针发现卵巢癌6号染色体存在洛缺失。我们研究了29个卵巢癌与19个探针定位到染色体6。29个肿瘤中有16个在6 q上表现出洛杂合性缺失（55%）。在这16例患者中，63%的患者显示该臂上的所有信息标记丢失。1例肿瘤显示6 q24-qter丢失，将假定的肿瘤抑制基因定位于该区域。6p的损失为28%。然而，使用来自6p的三个二核苷酸重复引物对来研究七个选定肿瘤中的洛缺失，证明在6p22.3-pter和6p 12 - 6p 22处均存在洛缺失。这些结果证实6 q含有与卵巢癌相关的肿瘤抑制基因，并表明6 p上也可能存在类似的基因。通过Southern分析，没有证据表明位于6q25.1的雌激素受体基因发生了基因组重排。6 q的洛缺失在高级别肿瘤中较低级别肿瘤多见。我们的研究结果的相关性，以前的工作在卵巢癌和其他实体瘤进行了讨论。
Investigation of genetic changes in tumours by loss of heterozygosity (LOH) is a powerful technique for identifying chromosomal regions that may contain tumour suppressor genes. LOH has been described on chromosome 6 in ovarian carcinoma using restriction fragment length polymorphism analysis with a small number of probes. We studied 29 ovarian carcinomas with 19 probes mapping to chromosome 6. Sixteen of the 29 tumours showed LOH on 6q (55%). Of these 16, 63% showed loss of all informative markers on that arm. One tumour showed loss of 6q24-qter, localising the putative tumour suppressor gene to that region. Loss on 6p was 28% overall. However, using three dinucleotide repeat primer pairs from 6p to study LOH in seven selected tumours, LOH was demonstrated at both 6p22.3-pter and at 6p12-6p22. These results confirm that 6q harbours a tumour suppressor gene of relevance to ovarian carcinoma and suggest that there may also be a similar gene(s) on 6p. By Southern analysis, there was no evidence of genomic rearrangements of the oestrogen receptor gene, located at 6q25.1. LOH on 6q was more common in high than low grade tumours. The relevance of our findings to previous work in ovarian cancer and other solid tumours is discussed.