Fujiwara Y, Chi D D, Wang H, Keleman P, Morton D L, Turner R, Hoon D S
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Cancer Res. 1999 Apr 1;59(7):1567-71.
Multiple DNA microsatellites with frequent loss of heterozygosity (LOH) in melanomas have been demonstrated. The finding that free DNA is enriched in blood of melanoma patients prompted studies to determine whether tumor-specific DNA, such as DNA microsatellites exhibiting LOH, can be detected in blood and have clinical use. In this study, 57 advanced and 19 early clinically staged melanoma patients were assessed using 10 microsatellite markers on six chromosomes. Matched plasma and melanoma tissues from 40 patients showed significant concordance of LOH (P < 0.0001). The frequency of LOH microsatellite markers detected in plasma significantly increased in more advanced-staged patients. At locus D3S1293, LOH detection showed significant correlation to clinical disease progression (P = 0.02). Additionally, the combination of LOH microsatellite markers D9S157 and D3S1293 (P = 0.01), D9S157 and D1S228 (P = 0.05), and D11S925 and D3S1293 (P = 0.01) were significantly correlated to progression of different clinical stages of disease. These studies indicate that tumor-specific LOH markers in plasma have a potential clinical use as diagnostic and prognostic markers in melanoma patients.
在黑色素瘤中已证实存在多个杂合性频繁缺失（LOH）的DNA微卫星。黑色素瘤患者血液中游离DNA含量丰富这一发现促使人们开展研究，以确定能否在血液中检测到肿瘤特异性DNA，如表现出LOH的DNA微卫星，并将其用于临床。在本研究中，使用位于6条染色体上的10个微卫星标记对57例晚期和19例早期临床分期的黑色素瘤患者进行了评估。40例患者的配对血浆和黑色素瘤组织显示出LOH的显著一致性（P < 0.0001）。在血浆中检测到的LOH微卫星标记的频率在分期更晚的患者中显著增加。在D3S1293位点，LOH检测与临床疾病进展显著相关（P = 0.02）。此外，LOH微卫星标记D9S157和D3S1293（P = 0.01）、D9S157和D1S228（P = 0.05）以及D11S925和D3S1293（P = 0.01）的组合与疾病不同临床分期的进展显著相关。这些研究表明，血浆中的肿瘤特异性LOH标记物在黑色素瘤患者中具有作为诊断和预后标记物的潜在临床应用价值。
