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Absence of Genetic Alteration at Codon 531 of the Human c-src Gene in 479 Advanced Colorectal Cancers from Japanese and Caucasian Patients¹

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato, Tokyo 108-8639, Japan [Y. D., Y. F., T. K., H. I., M. F., Y. N.]; Japanese Foundation for Cancer Research, Toshima, Tokyo 170-8455, Japan [S. S.]; The Second Department of Surgery, Osaka University Medical School, Suita City, Osaka 565-0871, Japan [S. N.]; and Department of Surgery, Leiden University Medical Center, 2300 RC, Leiden, the Netherlands [G-J. L., R. A. E. M. T., C. J. H. v. d. V.]

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.

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