Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients

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 underg one any genetic changes. However, recently truncating mutations at codon 53 1 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, tu morigenic, and metastasis promoting. To investigate whether the codon 531-s pecific mutation could be involved in the carcinogenesis of colorectal canc er in the Japanese and Caucasian populations, we examined a total of 479 ad vanced 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 conforma tion polymorphism analysis, we detected no genetic alteration in any of the advanced colorectal cancers. Our results suggest that the codon 531-specif ic mutational activation of c-src is unlikely to play a significant role in the malignant progression of colorectal cancers among most Japanese and Ca ucasian patients.