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Lab-on-Disk Platform for KRAS Mutation Testing

  • Iemmolo Rosario
  • Guarnaccia Maria
  • Petralia Salvatore
  • Cavallaro Sebastiano
  • Conoci SabrinaEmail author
Conference paper
Part of the Lecture Notes in Electrical Engineering book series (LNEE, volume 539)

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. In the United States is currently the third deadliest cancer with more than 1 million patients diagnosed annually of which 50% will develop metastatic disease. In some subtypes of CRC, the KRAS mutation status has emerged as an important diagnostic/prognostic marker for the response to treatment with anti-EGFR drugs in patients with metastatic CRC. Currently, the direct sequencing remains the gold standard technique for the diagnosis of DNA mutations, but the low sensitivity, time-consuming and the need for operating in rooms with dedicated instrumentation makes this method disadvantageous in daily practice. In recent years, new technologies characterized by different sensitivities, specificities and complexities are starting to be used in research and clinical studies for the detection of DNA genotyping. In this work, we propose a novel portable Lab-on-Disk platform developed by STMicroelectronics as a competitive device able to perform TaqMan-based real-time PCR for the rapid and simultaneous detection and identification of KRAS gene mutations.

Keywords

Optical biosensor Colorectal cancer Diagnostics RtPCR DNA mutations 

References

  1. 1.
    Kim, H.S., et al.: The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: a retrospective analysis. BMC Cancer 16, 120 (2016)CrossRefGoogle Scholar
  2. 2.
    Siegel, R.L., Miller, K.D., Jemal, A.: Cancer statistics, 2018. CA Cancer J. Clin. 68(1), 7–30 (2018)CrossRefGoogle Scholar
  3. 3.
    Schweiger, M.R., et al.: Genomics and epigenomics of colorectal cancer. Wiley Interdiscip. Rev. Syst. Biol. Med. 5(2), 205–219 (2013)CrossRefGoogle Scholar
  4. 4.
    Chubb, D., et al.: Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing. J. Clin. Oncol. 33(5), 426–432 (2015)CrossRefGoogle Scholar
  5. 5.
    Boland, P.M., Yurgelun, M.B., Boland, C.R.: Recent progress in Lynch syndrome and other familial colorectal cancer syndromes. CA Cancer J. Clin. (2018)Google Scholar
  6. 6.
    Jancik, S., et al.: Clinical relevance of KRAS in human cancers. J. Biomed. Biotechnol. 2010, 150960 (2010)CrossRefGoogle Scholar
  7. 7.
    Dienstmann, R., Vilar, E., Tabernero, J.: Molecular predictors of response to chemotherapy in colorectal cancer. Cancer J. 17(2), 114–126 (2011)CrossRefGoogle Scholar
  8. 8.
    De Roock, W., et al.: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11(8), 753–762 (2010)Google Scholar
  9. 9.
    Knickelbein, K., Zhang, L.: Mutant KRAS as a critical determinant of the therapeutic response of colorectal cancer. Genes Dis. 2(1), 4–12 (2015)CrossRefGoogle Scholar
  10. 10.
    Mariani, P., et al.: Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis. Anticancer Res. 30(10), 4229–4235 (2010)Google Scholar
  11. 11.
    Zenonos, K., Kyprianou, K.: RAS signaling pathways, mutations and their role in colorectal cancer. World J. Gastrointest. Oncol. 5(5), 97–101 (2013)CrossRefGoogle Scholar
  12. 12.
    Eser, S., et al.: Oncogenic KRAS signalling in pancreatic cancer. Br. J. Cancer 111(5), 817–822 (2014)CrossRefGoogle Scholar
  13. 13.
    Garassino, M.C., et al.: Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann. Oncol. 22(1), 235–237 (2011)CrossRefGoogle Scholar
  14. 14.
    Jones, R.P., et al.: Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br. J. Cancer 116(7), 923–929 (2017)CrossRefGoogle Scholar
  15. 15.
    Shackelford, R.E., et al.: KRAS testing: a tool for the implementation of personalized medicine. Genes Cancer 3(7–8), 459–466 (2012)CrossRefGoogle Scholar
  16. 16.
    Giamblanco, N., et al.: Ionic strength-controlled hybridization and stability of hybrids of KRAS DNA single-nucleotides: a surface plasmon resonance study. Coll. Surf. B 158, 41–46 (2017)CrossRefGoogle Scholar
  17. 17.
    Guedes, J.G., et al.: High resolution melting analysis of KRAS, BRAF and PIK3CA in KRAS exon 2 wild-type metastatic colorectal cancer. BMC Cancer 13, 169 (2013)CrossRefGoogle Scholar
  18. 18.
    Foglieni, B., et al.: Integrated PCR amplification and detection processes on a Lab-on-Chip platform: a new advanced solution for molecular diagnostics. Clin. Chem. Lab. Med. 48(3), 329–336 (2010)CrossRefGoogle Scholar
  19. 19.
    Petralia, S., et al.: Silicon nitride surfaces as active substrate for electrical DNA biosensors. Sens. Actuators B Chem. 252, 492–502 (2017)CrossRefGoogle Scholar
  20. 20.
    Petralia, S., Conoci, S.: PCR technologies for point of care testing: progress and perspectives. ACS Sens. 2(7), 876–891 (2017)CrossRefGoogle Scholar
  21. 21.
    Petralia, S., Sciuto, E.L., Conoci, S.: A novel miniaturized biofilter based on silicon micropillars for nucleic acid extraction. Analyst 142(1), 140–146 (2017)CrossRefGoogle Scholar
  22. 22.
    International drug monitoring: the role of national centres. Report of a WHO meeting. World Health Organ Technical Report Series, vol. 498, p. 1–25 (1972)Google Scholar
  23. 23.
    Petralia, S., et al.: A miniaturized silicon based device for nucleic acids electrochemical detection. Sens. Bio-Sens. Res. 6, 90–94 (2015)CrossRefGoogle Scholar
  24. 24.
    Petralia, S., et al.: An innovative chemical strategy for PCR-free genetic detection of pathogens by an integrated electrochemical biosensor. Analyst 142(12), 2090–2093 (2017)CrossRefGoogle Scholar
  25. 25.
    Guarnaccia, M., et al.: Miniaturized real-time PCR on a Q3 system for rapid KRAS genotyping. Sensors (Basel) 17(4) (2017)CrossRefGoogle Scholar
  26. 26.
    Kranenburg, O.: The KRAS oncogene: past, present, and future. Biochimica et Biophysica Acta (BBA)—Rev. Cancer 1756(2), 81–82 (2005)CrossRefGoogle Scholar
  27. 27.
    Amado, R.G., et al.: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26(10), 1626–1634 (2008)CrossRefGoogle Scholar
  28. 28.
    Neumann, J., et al.: Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol. Res. Pract. 205(12), 858–862 (2009)CrossRefGoogle Scholar
  29. 29.
    Sinicrope, F.A., et al.: Association of dna mismatch repair and mutations in braf and KRAS with survival after recurrence in stage III colon cancers: a secondary analysis of 2 randomized clinical trials. JAMA Oncol. 3(4), 472–480 (2017)CrossRefGoogle Scholar
  30. 30.
    Khan, S.A., et al.: EGFR gene amplification and KRAS mutation predict response to combination targeted therapy in metastatic colorectal cancer. Pathol. Oncol. Res. 23(3), 673–677 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Neurological Sciences—Italian National Research CouncilCataniaItaly
  2. 2.STMicroelectronicsCataniaItaly

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