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Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis

  • Review
  • Published:
Tumor Biology

Abstract

Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.

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Authors and Affiliations

  1. Oncology Unit 2, Azienda Ospedaliera–Universitaria Pisana, Ospedale Santa Chiara, Pisa, 56126, Italy

    Federica Zoratto

  2. Oncology Unit, ICOT, Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University, Latina, 04100, Italy

    Luigi Rossi, Monica Verrico, Anselmo Papa, Giuseppe Lo Russo & Silverio Tomao

  3. Oncology Unit, Ospedale San Carlo, Potenza, 85100, Italy

    Enrico Basso

  4. Gastroenterology Division, Ospedale Nuovo Regina Margherita, Rome, 00161, Italy

    Angelo Zullo

  5. Biostatistics and Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy

    Luigi Tomao

  6. Oncology Unit, “Sapienza” University, Ospedale Sant’Andrea, Rome, 00189, Italy

    Adriana Romiti

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  1. Federica Zoratto
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  2. Luigi Rossi
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  3. Monica Verrico
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  4. Anselmo Papa
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  7. Luigi Tomao
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  8. Adriana Romiti
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  9. Giuseppe Lo Russo
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  10. Silverio Tomao
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Correspondence to Federica Zoratto.

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Zoratto, F., Rossi, L., Verrico, M. et al. Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis. Tumor Biol. 35, 6195–6206 (2014). https://doi.org/10.1007/s13277-014-1845-9

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  • DOI: https://doi.org/10.1007/s13277-014-1845-9

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