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目的:研究肝癌1号染色体等位基因杂合性缺失(Lossofheterozygosity,LOH)及其临床意义。方法:采用PCR及微卫星多态性技术,对65例肝癌1号染色体上28个微卫星标志位点杂合性缺失进行检测。结果:65例肝癌中63例为杂合子,57例至少在1个微卫星标志位点上发生LOH,1号染色体LOH率为91%(57/63),1p76%(48/63),1q88%(5/59);1p36.32-p36.33和1q12~42区域内各微卫星标志LOH均在30%以上。微卫星标志LOH与性别、年龄、乙型肝炎病毒感染、肿瘤大小、包膜、血清AFP浓度、Edmonson分型均无关。D1S468和D1S2797LOH与肝癌根治术后3年内转移和复发有关,有D1S468(1p36.33)LOH者术后转移、复发率较无D1S468LOH者高(分别为82%和38%,P<0.05);有D1S2797(1p32)LOH者术后转移、复发率较无D1S2797LOH者高(分别为75%和37%,P<0.05)。1p、1q及各微卫星标志位点LOH均与肝癌术后生存率无关。结论:肝癌中存在1p36.32-p36.33和1q12~42的高频LOH,其中后者为首次报道;1p36.33和1p32区域内可能存在与肝癌转移、复发有关的肿瘤抑制基因。
Objective: To study the loss of heterozygosity (LOH) in the chromosome 1 allele of liver cancer and its clinical significance. Methods: The heterozygosity of 28 microsatellite loci on chromosome 1 in 65 cases of liver cancer was detected by PCR and microsatellite polymorphism. RESULTS: Among 65 cases of liver cancer, 63 were heterozygous and 57 cases had LOH at least on one microsatellite marker site. The LOH rate of chromosome 1 was 91% (57/63), 1p76% (48/63), 1q88. The LOH of all microsatellite markers in the area of %(5/59);1p36.32-p36.33 and 1q12-42 were all above 30%. The microsatellite marker LOH was not associated with sex, age, hepatitis B virus infection, tumor size, envelope, serum AFP concentration, and Edmonson classification. D1S468 and D1S2797LOH were associated with metastasis and recurrence within 3 years after radical resection of HCC. Patients with D1S468 (1p36.33) had higher postoperative metastasis and recurrence rate than those without D1S468LOH (82% and 38%, respectively, P<0.05). Patients with D1S2797 (1p32) LOH had higher postoperative metastasis and recurrence rates than those without D1S2797LOH (75% and 37%, respectively, P<0.05). The LOH of 1p, 1q and all microsatellite marker sites were not related to the survival rate of HCC. Conclusions: High-frequency LOH of 1p36.32-p36.33 and 1q12-42 exist in HCC, and the latter is the first report; 1p36.33 and 1p32 regions may have tumor suppressor genes associated with liver cancer metastasis and recurrence.