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Pattern of clinically relevant mutations in consecutive series of Russian colorectal cancer patients

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Abstract

One hundred and ninety-five consecutive surgically treated Russian colorectal cancer (CRC) patients were retrospectively analyzed for the presence of mutations in KRAS, NRAS, BRAF and PIK3CA genes as well as for the microsatellite instability status. Comparison between high-resolution melting analysis, co-amplification at lower denaturation temperature PCR, DNA sequencing and allele-specific PCR for the detection of KRAS codon 12/13 mutations revealed that none of these methods alone provided satisfactory results in 100 % of the analyzed cases; this experience supports the use of more than one mutation-detecting technique at least in some circumstances. KRAS codon 12/13 substitutions were detected in 70 (35.9 %) CRC cases. Other mutations in the RAS/RAF genes occurred in 22 (11.3 %) cases and included rare KRAS (n = 6), NRAS (n = 8) and BRAF (n = 8) alterations. 5 BRAF mutations affected codon 600, while the remaining 3 potentially functional substitutions were located in the position 594. Twenty-four (12.3 %) CRC cases carried mutations in the PIK3CA, and 18 of these tumors also contained activating alteration in the RAS/RAF genes (p = 0.007). Only 3 (1.5 %) CRC cases showed high-level microsatellite instability (MSI-H) as determined by a panel of mononucleotide markers. Overall, the distribution of potentially predictive mutations in Russian CRC cases is similar to the one observed in other patient series of European descent. Noticeable occurrence of D594G mutation in BRAF oncogene and low frequency of MSI-H may deserve specific attention.

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Acknowledgments

This work has been supported by the Russian Foundation for Basic Research (Grants 11-04-01643, 12-04-00535, 12-04-00928 and 12-04-31576), Russian Ministry of Education and Science (contract 14.512.11.0041), the Dynasty Foundation (contract 18/13), the President’s Research Council for Support of Young Russian Scientists (fellowships 768.2012.4 and 790.2012.4) and the Grant from Amgen Inc. (Thousand Oaks, CA).

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  1. Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, 197758, St.-Petersburg, Russia

    Grigoriy A. Yanus, Anna V. Belyaeva, Alexandr O. Ivantsov, Ekatherina Sh. Kuligina, Evgeny N. Suspitsin, Natalia V. Mitiushkina, Svetlana N. Aleksakhina, Aglaya G. Iyevleva, Olga A. Zaitseva, Olga S. Yatsuk, Tatiana V. Gorodnova, Tatiana N. Strelkova, Sofia A. Efremova, Alla Yu. Lepenchuk, Altn N. Ochir-Garyaev, Moisey B. Paneyah, Dmitriy E. Matsko, Alexandr V. Togo & Evgeny N. Imyanitov

  2. St.-Petersburg Pediatric Medical University, St.-Petersburg, 194100, Russia

    Grigoriy A. Yanus, Evgeny N. Suspitsin, Aglaya G. Iyevleva, Sofia A. Efremova, Alla Yu. Lepenchuk, Altn N. Ochir-Garyaev, Moisey B. Paneyah, Alexandr V. Togo & Evgeny N. Imyanitov

  3. I.I. Mechnikov North-Western Medical University, St-Petersburg, 191015, Russia

    Evgeny N. Imyanitov

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  1. Grigoriy A. Yanus
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Correspondence to Evgeny N. Imyanitov.

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Yanus, G.A., Belyaeva, A.V., Ivantsov, A.O. et al. Pattern of clinically relevant mutations in consecutive series of Russian colorectal cancer patients. Med Oncol 30, 686 (2013). https://doi.org/10.1007/s12032-013-0686-5

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