Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients.
Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients.
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发表时间：
1999-09
期刊：
影响因子：
11.2
通讯作者：
Y. Daigo;Yoichi Furukawa;T. Kawasoe;Hideyuki Ishiguro;Manabu Fujita;S. Sugai;Shoji Nakamori;G. Liefers;R. A. Tollenaar;Cornelis J.H. van de Velde;Yusuke Nakamura
中科院分区：
文献类型：
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作者：
Y. Daigo;Yoichi Furukawa;T. Kawasoe;Hideyuki Ishiguro;Manabu Fujita;S. Sugai;Shoji Nakamori;G. Liefers;R. A. Tollenaar;Cornelis J.H. van de Velde;Yusuke Nakamura
c-src是一种在序列上与劳斯肉瘤病毒的v-src基因同源的细胞人类基因，其激活被认为在几种类型的人类癌症的进展中起重要作用，而没有经历任何遗传变化。然而，最近报道了12%的晚期结肠癌中c-src基因531密码子的截短突变，并且还证明了这种改变具有激活、转化、致瘤和促进转移的作用。为了研究密码子531特异性突变是否与日本人和高加索人结直肠癌的发生有关，我们检查了421例日本患者（其中46例伴有肝或肺转移）和58例高加索人患者（其中11例伴有肝转移）的479例晚期结直肠癌。使用PCR-RFLP分析和额外的单链构象多态性分析，我们没有发现任何晚期结直肠癌的遗传变异。我们的研究结果表明，密码子531特异性突变激活的c-src是不太可能发挥重要作用，在大多数日本人和高加索人的结直肠癌的恶性进展。
Activation of c-src, a cellular human gene homologous in sequence to the v-src gene of Rous sarcoma virus, had been thought to play an important role in the progression of several types of human cancers, without having undergone any genetic changes. However, recently truncating mutations at codon 531 of the c-src gene were reported in 12% of the advanced colon cancers, and it was also demonstrated that this change was activating, transforming, tumorigenic, and metastasis promoting. To investigate whether the codon 531-specific mutation could be involved in the carcinogenesis of colorectal cancer in the Japanese and Caucasian populations, we examined a total of 479 advanced colorectal cancers from 421 Japanese patients (46 of them with liver or lung metastases) and from 58 Caucasian patients (11 of them with liver metastases). Using the PCR-RFLP assay and additional single-strand conformation polymorphism analysis, we detected no genetic alteration in any of the advanced colorectal cancers. Our results suggest that the codon 531-specific mutational activation of c-src is unlikely to play a significant role in the malignant progression of colorectal cancers among most Japanese and Caucasian patients.