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n South African Medical Journal - K-ras codon 12 and not TP53 mutations are predominant in advanced colorectal cancers : research
Background. Colorectal cancer (CRC) is one of the most common types of cancer, affecting 3 - 5% of the global population. K-ras proto-oncogene and TP53 tumour suppressor gene mutations are among the most common genetic alterations detected in advanced colorectal tumours.
Objective. To investigate the role of K-ras codon 12 and TP53 exons 5 - 9 mutations in late-stage CRC patients.
Methods. Blood samples were collected from 249 CRC patients, of whom 147 presented with advanced carcinoma. K-ras codon 12 mutations were analysed using polymerase chain reaction-restriction fragment length polymorphism, while direct sequencing was used in screening for TP53 exons 5 - 9 mutations.
Results. No significant changes were observed in TP53 exons 5 - 9, except for two cases in which nucleotide replacements were observed in the non-coding regions in intron 4 (c.376-19C>T) and intron 9 (c.993+12T>C). Heterozygous mutations in K-ras codon 12 were observed in 79 individuals suffering from advanced CRC (53.7%). Colon and rectal tumours were equally distributed among the heterozygotes, but colon tumours were mostly present in wild-type homozygotes (84.6%). There was also a predominance of Caucasians among heterozygotes and a predominance of Asians among the wild-type homozygotes.
Conclusion. Analysis of peripheral blood samples of CRC patients suffering from advanced carcinoma has prognostic value only for K-ras codon 12 mutations, and not for TP53 mutations.
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