Walker G J, Palmer J M, Walters M K, Nancarrow D J, Parsons P G, Hayward N K
Queensland Cancer Fund Research Unit, Joint Experimental Oncology Program, Queensland Institute of Medical Research, Herston, Australia.
Oncogene. 1994 Mar;9(3):819-24.
Various lines of evidence including linkage analysis, frequent homozygous and heterozygous deletions in melanoma DNAs, and the finding of a patient with multiple primary melanomas who harbours a 5p/9p translocation involving loss of several 9p markers, have indicated that the 9p22-p13 region harbours a gene important for the development of melanoma (MLM). We have used eight short tandem repeat polymorphism (STRP) markers mapping to this region to look for allelic losses in DNA from melanoma biopsies and cell lines. Heterozygous losses were found in 8/14 (57%) fresh melanoma biopsy DNAs with the smallest region of overlap (SRO) being between IFNA and D9S169. In addition, when DNA from 30 melanoma cell lines was studied, four cell lines (13%) were found to be homozygously deleted for various 9p markers. Two of these cell lines define the borders of overlapping homozygous deletions within a 4cM region of 9p21 between IFNA and D9S171. Moreover, a further 14 melanoma cell lines were hemizygous for the IFNA/D9S171/D9S126 region. These data support the hypothesis that the MLM gene acts as a tumour suppressor, and provide a refinement of its localization on 9p.
包括连锁分析、黑色素瘤DNA中频繁出现的纯合和杂合缺失，以及发现一名患有多发性原发性黑色素瘤的患者携带涉及多个9p标记缺失的5p/9p易位在内的各种证据表明，9p22-p13区域含有一个对黑色素瘤（MLM）发生发展至关重要的基因。我们使用了定位到该区域的8个短串联重复多态性（STRP）标记，来寻找黑色素瘤活检组织和细胞系DNA中的等位基因缺失情况。在14份新鲜黑色素瘤活检组织DNA中，有8份（57%）发现杂合缺失，最小重叠区域（SRO）位于IFNA和D9S169之间。此外，在研究30个黑色素瘤细胞系的DNA时，发现有4个细胞系（13%）的各种9p标记发生了纯合缺失。其中两个细胞系确定了9p21中IFNA和D9S171之间4cM区域内重叠纯合缺失的边界。此外，另有14个黑色素瘤细胞系在IFNA/D9S171/D9S126区域为半合子状态。这些数据支持了MLM基因作为肿瘤抑制基因的假说，并对其在9p上的定位进行了优化。
