Smeds J, Kumar R, Rozell B L, Hemminki K
Department of Biosciences, Karolinska Institute, Novum, 141 57 Huddinge and Department of Pathology, Huddinge University Hospital, 141 86 Huddinge, Sweden.
Mutagenesis. 2000 May;15(3):257-60. doi: 10.1093/mutage/15.3.257.
We carried out statistical analysis of the frequency of loss of heterozygosity (LOH) at 10 microsatellite markers on chromosome 9. In 44 microdissected sporadic primary melanomas a comparison of LOH frequency data with other patient data, like age at diagnosis and tumour thickness, showed an interesting correlation between patient age at diagnosis and frequency of LOH on chromosome 9. The patient group with age >72 years at diagnosis (n = 22, mean age 82.3 +/- 6.0 years, mean LOH 3.4 +/- 2.3) showed significantly increased LOH frequency (OR 3.1, 95% CI 1.8-5.3; chi(2) test, P < 0.0001) compared with age group </=72 years (n = 22, mean age 56.1 +/- 14.5 years, mean LOH 1.8 +/- 1.7). A statistically significant increased frequency of LOH (OR 3.5, 95% CI 1.5-7.9; chi(2) test, P = 0.03 after Bonferroni correction) was found only at marker D9S736 on 9p22 (telomeric to the INK4-ARF locus) relative to other markers on six different chromosomes. No other marker, including those located within the INK4-ARF locus, showed a statistically significant increased frequency of LOH. Our results for the first time show a non-random tendency for increased allelic loss in melanomas with increased patient age at diagnosis, besides supporting the existence of an additional tumour suppressor gene(s) on chromosome 9.
我们对9号染色体上10个微卫星标记的杂合性缺失(LOH)频率进行了统计分析。在44例显微切割的散发性原发性黑色素瘤中,将LOH频率数据与其他患者数据(如诊断时年龄和肿瘤厚度)进行比较,结果显示诊断时患者年龄与9号染色体上的LOH频率之间存在有趣的相关性。诊断时年龄>72岁的患者组(n = 22,平均年龄82.3±6.0岁,平均LOH 3.4±2.3)与年龄≤72岁的患者组(n = 22,平均年龄56.1±14.5岁,平均LOH 1.8±1.7)相比,LOH频率显著增加(OR 3.1,95% CI 1.8 - 5.3;卡方检验,P < 0.0001)。相对于六个不同染色体上的其他标记,仅在9p22上的标记D9S736(位于INK4 - ARF基因座的端粒侧)发现LOH频率有统计学意义的增加(OR 3.5,95% CI 1.5 - 7.9;卡方检验,经Bonferroni校正后P = 0.03)。包括位于INK4 - ARF基因座内的那些标记在内,没有其他标记显示LOH频率有统计学意义的增加。我们的结果首次表明,除了支持9号染色体上存在额外的肿瘤抑制基因外,黑色素瘤中随着诊断时患者年龄增加,等位基因缺失有非随机增加的趋势。