Kubo A, Yoshikawa A, Hirashima T, Masuda N, Takada M, Takahara J, Fukuoka M, Nakagawa K
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
Cancer Res. 1996 Mar 15;56(6):1232-6.
Reverse transcription-PCR-single-strand conformation polymorphism analysis was performed to detect topoisomerase IIalpha mutations using total RNA from 19 bronchial biopsy specimens obtained from 13 patients with small cell lung cancer. An abnormally migrating single-strand conformation polymorphism band was observed in one tumor sample from a patient treated with etoposide-containing chemotherapy. DNA sequence analysis of this tumor showed two transversions at codons 486 (G to A) and 494 (A to G), resulting in two missense mutations (Arg to Lys and Glu to Gly, respectively). The codon 486 mutation was identical to that previously found in two cell lines selected for amsacrine resistance. These results demonstrate that mutations of topoisomerase IIalpha occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.
利用从13例小细胞肺癌患者获取的19份支气管活检标本的总RNA，进行逆转录聚合酶链反应-单链构象多态性分析以检测拓扑异构酶IIα突变。在1例接受含依托泊苷化疗的患者的肿瘤样本中观察到异常迁移的单链构象多态性条带。对该肿瘤的DNA序列分析显示密码子486（G到A）和494（A到G）发生了两个颠换，分别导致两个错义突变（分别为Arg到Lys和Glu到Gly）。密码子486突变与先前在两个选择用于阿霉素抗性的细胞系中发现的突变相同。这些结果表明拓扑异构酶IIα突变发生在小细胞肺癌患者中。这些突变在对依托泊苷耐药性发展中的意义需要进一步研究。
