Kishimoto Y, Sugio K, Mitsudomi T, Oyama T, Virmani A K, McIntire D D, Gazdar A F
Department of Pathology, University of Texas, Southwestern Medical Center at Dallas 75235-8593, USA.
J Cancer Res Clin Oncol. 1995;121(5):291-6. doi: 10.1007/BF01209596.
We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC) including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in squamous cell carcinoma (17 of 29 informative cases or 59%), and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports, we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.
我们分析了87例日本非小细胞肺癌(NSCLC),其中包括30例鳞状细胞癌、51例腺癌和6例大细胞癌,检测9号染色体短臂上的杂合性缺失(LOH),并将我们的研究结果与临床病理特征相关联。我们使用了位于9p上的四个多态微卫星标记(干扰素A基因、D9S171、D9S126和D9S169),这些标记位于肺癌相关的关键区域(9p21 - 22)两侧。我们观察到NSCLC中9p处的DNA序列改变(82例信息性病例中有27例,占33%)。四个标记之间的一致性很高(87%),表明缺失通常相对较大。在9p上观察到的27个基因改变包括26例LOH、1例纯合缺失和1例具有LOH且有微卫星改变证据(以条带迁移率改变为特征)的病例。我们注意到9p处LOH的频率很高,尤其是在鳞状细胞癌中(29例信息性病例中有17例,占59%),以及在低分化NSCLC中(23例信息性病例中有12例,占52%)。9p处的LOH与其他临床参数之间没有相关性,包括生存、性别、肿瘤大小以及区域或远处转移的存在。与其他报告相反,我们仅发现罕见的纯合缺失实例(1%),微卫星改变表现为迁移率改变的情况(1%)。我们的研究结果表明,9号染色体短臂上的LOH与日本NSCLC患者的鳞状细胞癌和低分化癌相关。