Leggett B, Young J, Buttenshaw R, Thomas L, Young B, Chenevix-Trench G, Searle J, Ward M
Glaxo Gastroenterology Research Laboratory, Royal Brisbane Hospital Clinical Research Centre, Bancroft Centre, Australia.
Br J Cancer. 1995 May;71(5):1070-3. doi: 10.1038/bjc.1995.206.
Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in colorectal carcinomas. A number of known or putative tumour-suppressor genes including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of chromosome 17, and this region has not been extensively analysed in colorectal tumours. In this study 72 colorectal carcinomas were examined for allelic loss at eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus, which is known to be important in colorectal carcinoma, and also telomeric to p53 on 17p. Allelic loss continued to be present in more than 50% of cases in the pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22-23. The most telomeric markers on 17q showed lower rates of allelic loss. Analysis of cases with partial deletions which did not include the p53 locus showed a common region of overlap of the deletions centred on D17S40. This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this region.
等位基因缺失是结直肠癌中肿瘤抑制基因失活的常见机制。17号染色体长臂上存在许多已知或推定的肿瘤抑制基因,包括NF1、BRCA1、NME1、NME2和抑制素,而该区域在结直肠癌中尚未得到广泛分析。在本研究中,对72例结直肠癌进行了17号染色体上8个位点的等位基因缺失检测。在已知对结直肠癌很重要的p53位点以及17p上p53的端粒区域,等位基因缺失都很常见。在着丝粒周围区域以及17q近端至17q22 - 23处的标记LEW101(D17S40),超过50%的病例中仍存在等位基因缺失。17q上最末端的标记显示出较低的等位基因缺失率。对不包括p53位点的部分缺失病例进行分析,发现缺失的共同重叠区域以D17S40为中心。这表明17q上等位基因缺失的靶点是该区域的一个肿瘤抑制基因。