Lee D J, Koch W M, Yoo G, Lango M, Reed A, Califano J, Brennan J A, Westra W H, Zahurak M, Sidransky D
Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Hospital, Baltimore, Maryland 21205, USA.
Clin Cancer Res. 1997 Apr;3(4):501-5.
We screened 73 primary head and neck squamous cell carcinoma (HNSCC) specimens for loss of heterozygosity (LOH) on chromosome 14q. Analysis of 20 polymorphic microsatellite markers identified 29 (40%) HNSCCs exhibiting LOH of 14q in at least one locus. Six tumors had probable monosomy of 14q, displaying allelic loss for all informative markers tested, and 23 demonstrated partial losses on 14q. Fine mapping with 1-10 additional markers revealed two poorly defined regions of loss (4-7 cM) at 14q13-21 and 14q31-32.1 in seven tumors. In 53 patients with previously untreated tumors treated with curative intent, LOH of 14q in these tumors correlated with poor survival. Compared to patients with tumors that retain heterozygosity of 14q, those with 14q LOH had a 3-fold increased risk of death in multivariate analysis (hazards ratio, 3.2; 95% confidence interval = 1.2-8.4). These data have confirmed a high frequency of chromosome 14q loss in HNSCC and suggest that LOH of any region on chromosome 14q is an indicator of poor outcome.
我们对73例原发性头颈部鳞状细胞癌（HNSCC）标本进行了14号染色体长臂杂合性缺失（LOH）筛查。通过分析20个多态性微卫星标记，发现29例（40%）HNSCC在至少一个位点存在14号染色体长臂的杂合性缺失。6个肿瘤可能存在14号染色体长臂单体型，对所有检测的信息性标记均显示等位基因缺失，23个肿瘤显示14号染色体长臂部分缺失。使用另外1 - 10个标记进行精细定位，在7个肿瘤中发现14q13 - 21和14q31 - 32.1存在两个边界不清的缺失区域（4 - 7 cM）。在53例接受根治性治疗的初治肿瘤患者中，这些肿瘤中14号染色体长臂的杂合性缺失与不良生存相关。与14号染色体长臂保持杂合性的肿瘤患者相比，14号染色体长臂杂合性缺失的患者在多因素分析中死亡风险增加3倍（风险比，3.2；95%置信区间 = 1.2 - 8.4）。这些数据证实了HNSCC中14号染色体长臂缺失的高频率，并表明14号染色体长臂上任何区域的杂合性缺失都是预后不良的指标。
