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Analysis of K-ras codon 12 and TP53 mutations in patients with advanced colorectal carcinoma

Gulnur Zhunussova, Leyla Djansugurova, Elmira Khussainova, Benazir Zhunusbekova, Georgiy Afonin, Dilyara Khaidarova, M Matejcic, M Iqbal Parker

Abstract


Background. Colorectal cancer (CRC) is one of the most common types of cancer, affecting 3 - 5% of the global population. K-ras protooncogene 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.


Authors' affiliations

Gulnur Zhunussova, Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Almaty, Kazakhstan

Leyla Djansugurova, Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Almaty, Kazakhstan

Elmira Khussainova, Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Almaty, Kazakhstan

Benazir Zhunusbekova, Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Almaty, Kazakhstan

Georgiy Afonin, Almaty Oncology Centre, Almaty, Kazakhstan

Dilyara Khaidarova, Almaty Oncology Centre, Almaty, Kazakhstan

M Matejcic, nternational Centre for Genetic Engineering and Biotechnology, Cape Town Component, South Africa, and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, South Africa

M Iqbal Parker, International Centre for Genetic Engineering and Biotechnology, Cape Town Component, South Africa, and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, South Africa

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Keywords

Colorectal cancer; TP53 mutations; K-ras mutations

Cite this article

South African Medical Journal 2015;105(8):670-674. DOI:10.7196/SAMJnew.7886

Article History

Date submitted: 2014-08-20
Date published: 2015-09-21

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