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Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design
Department Histopathology, King’s College Hospital and King’s Health Partners, Denmark Hill, London SE5 9RS, UK
Received: 2 December 2011; in revised form: 23 January 2012 / Accepted: 1 February 2012 / Published: 13 February 2012
Abstract: Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.
Keywords: neoplasm; tumor heterogeneity; topographic compartments; tumor microenvironment; tumor hypoxia; exosome; clonal expansion; cell segregation; tumor progression; metastasis
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MDPI and ACS Style
Diaz-Cano, S.J. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design. Int. J. Mol. Sci. 2012, 13, 1951-2011.
Diaz-Cano SJ. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design. International Journal of Molecular Sciences. 2012; 13(2):1951-2011.
Diaz-Cano, Salvador J. 2012. "Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design." Int. J. Mol. Sci. 13, no. 2: 1951-2011.