title: Tumour heterogeneity: principles and practical consequences.
abstract: Two major reasons compel us to study tumour heterogeneity: firstly, it represents the basis of acquired therapy resistance, and secondly, it may be one of the major sources of the low level of reproducibility in clinical cancer research. The present review focuses on the heterogeneity of neoplastic disease, both within the primary tumour and between primary tumour and metastases. We discuss different levels of heterogeneity and the current understanding of the phenomenon, as well as imminent developments relevant for clinical research and diagnostic pathology. It is necessary to develop new tools to study heterogeneity and new biomarkers for heterogeneity. Established and new in situ methods will be very useful. In future studies, not only clonal heterogeneity needs to be addressed but also non-clonal phenotypic heterogeneity which might be important for therapy resistance. We also review heterogeneity established in major tumour types, in order to explore potential similarities that might help to define new strategies for targeted therapy.
authors.affiliation: Department of Medical Sciences, University of Trieste, Strada di Fiume 447, Trieste, 34149, Italy. stanta@icgeb.org.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stanta
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Stephan Wenzel
authors.initials: SW
authors.lastname: Jahn
authors.affiliation: Department of Medical Sciences, University of Trieste, Strada di Fiume 447, Trieste, 34149, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bonin
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
mesh_terms: D000818:Animals; D000066670:Cell Plasticity / Q000502:physiology; D018740:Genetic Heterogeneity; D006801:Humans; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D010641:Phenotype; D015203:Reproducibility of Results
keywords: Clonal; Epigenetic; Functional plasticity; Intertumour; Intratumour; Molecular; Phenotypic; Spatial; Temporal; Tumour heterogeneity