Ninomiya H, Nomura K, Satoh Y, Okumura S, Nakagawa K, Fujiwara M, Tsuchiya E, Ishikawa Y
Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Br J Cancer. 2006 May 22;94(10):1485-91. doi: 10.1038/sj.bjc.6603121.
To investigate what kind of genetic instability plays important roles in lung carcinogenesis, we analyzed micro- and minisatellite instability, loss of heterozygosity (LOH) and chromosome instability in 55 cases of lung cancer, including, 10 squamous cell, 5 large cell, and 3 small cell carcinomas, and 37 adenocarcinomas. Analysis of minisatellite instability, the mechanism of which is different from microsatellite instability, has not been reported previously. Minisatellite instability was detected in only one case (1/55, 1.8%), and the frequency of microsatellite instability was low, being found only in three cases (3/55, 5.5%). In contrast, LOH, for at least in one locus, was observed in 27 cases (49.1%). In adenocarcinomas, the frequency of LOH was higher in poorly differentiated compared to more differentiated carcinomas. For chromosome instability, a similar correlation between differentiation grade and instability was observed in adenocarcinomas. And instability was more common in large cell and small cell carcinomas than in adenocarcinomas. Our analysis showed that chromosome instability and LOH, rather than mini- and microsatellite instability, play significant roles in the development of lung cancer.
为了研究哪种基因不稳定性在肺癌发生过程中起重要作用，我们分析了55例肺癌患者的微卫星和小卫星不稳定性、杂合性缺失（LOH）及染色体不稳定性，其中包括10例鳞状细胞癌、5例大细胞癌、3例小细胞癌以及37例腺癌。此前尚未有关于小卫星不稳定性分析的报道，其机制与微卫星不稳定性不同。仅在1例患者（1/55，1.8%）中检测到小卫星不稳定性，微卫星不稳定性的发生率较低，仅在3例患者（3/55，5.5%）中发现。相比之下，至少在一个位点观察到杂合性缺失的有27例（49.1%）。在腺癌中，低分化腺癌的杂合性缺失发生率高于高分化腺癌。对于染色体不稳定性，在腺癌中观察到分化程度与不稳定性之间存在类似的相关性。并且大细胞癌和小细胞癌中的不稳定性比腺癌更常见。我们的分析表明，在肺癌发生过程中起重要作用的是染色体不稳定性和杂合性缺失，而非小卫星和微卫星不稳定性。
