Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma.
Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma.
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发表时间：
1991-10
期刊：
影响因子：
11.2
通讯作者：
D. Millikin;E. Meese;B. Vogelstein;C. Witkowski;Jeffrey M. Trent
中科院分区：
文献类型：
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作者：
D. Millikin;E. Meese;B. Vogelstein;C. Witkowski;Jeffrey M. Trent
恶性黑色素瘤已被证实表现为6号染色体的反复异常，特别是长臂(6q)。应用限制性片段长度多态分析作为分子遗传学方法，检测6q染色体上的基因座构成杂合性缺失(LOH)。用识别6q方向限制性片段长度多态的5个DNA标记和识别6p的1个多态DNA标记，对20对自体肿瘤DNA和正常DNA进行筛选，以确定每个患者的肿瘤和构成基因类型。在53个信息性基因座中，有21个(40%)检测到6q染色体上的LOH。5名具有多个信息位点的患者的等位基因丢失与6号染色体的整个长臂(或整个拷贝)的丢失一致，而另外4名患者则表现出6q的末端缺失。标记基因c-myb和ESR(6q22-23和6q24-27)是6q等位基因缺失频率最高的区域(60%)。与6q缺失的频率相比，仅有5%的病例在其他四条染色体(1、11、16、17)上观察到LOH。这些结果使我们得出结论，在人类恶性黑色素瘤中，6号染色体长臂序列的丢失是一个非随机的、可能与生物学相关的事件。
Malignant melanoma has been documented to display recurring abnormalities of chromosome 6, particularly the long arm (6q). Restriction fragment length polymorphism analysis was used as a molecular genetic approach to examine loci on chromosome 6q for loss of constitutional heterozygosity (LOH). Five DNA markers that recognize restriction fragment length polymorphisms along 6q and one polymorphic DNA marker for 6p were used to screen 20 autologous pairs of tumor DNA and normal DNA to determine the tumor and constitutional genotypes of each patient. LOH on chromosome 6q was identified at 21 of 53 informative loci (40%). Five patients with more than one informative locus had allele losses consistent with the loss of the entire long arm (or of an entire copy) of chromosome 6, while four other patients demonstrated terminal deletions of 6q. The chromosomal region bearing the highest frequency of 6q allelic loss (60%) is defined by the marker loci c-MYB and ESR (6q22-23 and 6q24-27). In contrast to the frequency of 6q loss, LOH was observed at loci on four other chromosomes (1, 11, 16, 17) in only 5% of cases. These results have led us to conclude that the loss of sequences from the long arm of chromosome 6 is a nonrandom and possibly biologically relevant event in human malignant melanoma.