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Biochip detection of KRAS, BRAF, and PIK3CA somatic mutations in colorectal cancer patients

  • Genomics. Transcriptomics
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Abstract

Somatic mutations of KRAS, PIK3CA, and BRAF cause insensitivity of colorectal tumors to therapy with anti-EGFR monoclonal antibodies, necessitating a genetic testing prior to therapy. A biological microchip was developed and validated to allow detection of 19 somatic mutations in KRAS, PIK3CA, and BRAF genes. The method combines LNA-clamp PCR and allele-specific hybridization on a microchip and detects mutant DNA in 100 times wild-type background (1%). A total of 66 DNA samples isolated from colorectal tumors were tested with the biochip. Possible associations between the genetic status of the tumor and the patient’s characteristics (age, sex, tumor localization, stage, and TMN) were assessed statistically. KRAS mutations were more common in females (P = 0.02) and in patients with distant metastasis (P = 0.04). Other associations between the presence of mutations and patient characteristics were not observed. The method proved highly sensitive and can be used in oncology to select patients who sensitive to therapy with antiEGFR monoclonal antibodies.

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Abbreviations

KRAS :

Kirsten rat sarcoma viral oncogene homolog

PIK3CA :

phosphatidylinositol 3-kinase, catalytic α subunit

BRAF :

v-raf murine sarcoma viral oncogene homolog B

EGFR :

epidermal growth factor receptor

ERK:

extracellular signal-regulated kinase

mTOR:

mammalian target of rapamycin

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Authors and Affiliations

  1. BIOCHIP-IMB Ltd., Moscow, 117312, Russia

    M. A. Emelyanova & T. V. Nasedkina

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    M. A. Emelyanova & T. V. Nasedkina

  3. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    M. A. Emelyanova, F. A. Amossenko, A. V. Semyanikhina, V. A. Aliev, Yu. A. Barsukov & L. N. Lyubchenko

  4. Medical Genetic Research Center, Moscow, 115478, Russia

    F. A. Amossenko

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  1. M. A. Emelyanova
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  2. F. A. Amossenko
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  3. A. V. Semyanikhina
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  4. V. A. Aliev
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  5. Yu. A. Barsukov
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  6. L. N. Lyubchenko
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Correspondence to M. A. Emelyanova.

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Original Russian Text © M.A. Emelyanova, F.A. Amossenko, A.V. Semyanikhina, V.A. Aliev, Yu.A. Barsukov, L.N. Lyubchenko, T.V. Nasedkina, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 4, pp. 617–627.

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Emelyanova, M.A., Amossenko, F.A., Semyanikhina, A.V. et al. Biochip detection of KRAS, BRAF, and PIK3CA somatic mutations in colorectal cancer patients. Mol Biol 49, 550–559 (2015). https://doi.org/10.1134/S0026893315040032

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  • DOI: https://doi.org/10.1134/S0026893315040032

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