Tomizawa Yoshio, Iijima Hironobu, Nomoto Taisuke, Iwasaki Yasuki, Otani Yoshimi, Tsuchiya Satoshi, Saito Ryusei, Dobashi Kunio, Nakajima Takashi, Mori Masatomo
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Lung Cancer. 2004 Dec;46(3):305-12. doi: 10.1016/j.lungcan.2004.05.003.
We investigated the clinicopathological significance of aberrant methylation of the retinoic acid receptor-beta2 (RARbeta2), RAS association domain family 1A (RASSF1A) and fragile histidine triad (FHIT) genes located on choromosome 3p in 120 patients with primary non-small cell lung cancer (NSCLC) by a methylation-specific PCR method. Aberrant methylation of these was detected in 31 (26%), 35 (29%) and 43 (36%) tumors, respectively. There was no correlation with the methylation status of any of the genes. RARbeta2 methylation was more frequently observed in patients with a smoking history (19 of 61, 31%) than in patients without one (3 of 29, 10%, P = 0.0373). RARbeta2 methylation was also preferentially observed in advanced stage NSCLC (12 of 71 (17%) in stage I, 5 of 15 (33%) in stage II, 11 of 24 (46%) in stage III, and 3 of 8 (38%) in stage IV, P = 0.0057 (stage I versus II, III,and IV)). FHIT methylation was predominantly detected in tumors with vascular invasion (21 of 44, 48%, P = 0.0703) or lymphatic permeation (28 of 59, 47%, P = 0.0115). RASSF1A methylation was more frequently observed in adenocarcinomas (28 of 72, 39%) than in squamous cell carcinomas (6 of 45, 13%, P = 0.0033). These results indicate that aberrant methylation of the candidate tumor suppressor genes on 3p plays a respective role in the pathogenesis of NSCLC.
我们采用甲基化特异性聚合酶链反应方法，对120例原发性非小细胞肺癌（NSCLC）患者位于3号染色体上的维甲酸受体β2（RARβ2）、RAS关联结构域家族1A（RASSF1A）和脆性组氨酸三联体（FHIT）基因的异常甲基化的临床病理意义进行了研究。这些基因的异常甲基化分别在31例（26%）、35例（29%）和43例（36%）肿瘤中被检测到。这些基因的甲基化状态之间无相关性。有吸烟史的患者中RARβ2甲基化的发生率（61例中的19例，31%）高于无吸烟史的患者（29例中的3例，10%，P = 0.0373）。RARβ2甲基化也更常见于晚期NSCLC（I期71例中的12例（17%），II期15例中的5例（33%），III期24例中的11例（46%），IV期8例中的3例（38%），P = 0.0057（I期与II期、III期和IV期相比））。FHIT甲基化主要在有血管侵犯的肿瘤（44例中的21例，48%，P = 0.0703）或淋巴浸润的肿瘤（59例中的28例，47%，P = 0.0115）中被检测到。RASSF1A甲基化在腺癌（72例中的28例，39%）中比在鳞状细胞癌（45例中的6例，13%，P = 0.0033）中更常见。这些结果表明，3p上候选抑癌基因的异常甲基化在NSCLC的发病机制中各自发挥作用。
