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Biochim Biophys Acta. 2010 Jan;1805(1):105-17. doi: 10.1016/j.bbcan.2009.11.002. Epub 2009 Nov 18.

Tumor heterogeneity: causes and consequences.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

Abstract

With rare exceptions, spontaneous tumors originate from a single cell. Yet, at the time of clinical diagnosis, the majority of human tumors display startling heterogeneity in many morphological and physiological features, such as expression of cell surface receptors, proliferative and angiogenic potential. To a substantial extent, this heterogeneity might be attributed to morphological and epigenetic plasticity, but there is also strong evidence for the co-existence of genetically divergent tumor cell clones within tumors. In this perspective, we summarize the sources of intra-tumor phenotypic heterogeneity with emphasis on genetic heterogeneity. We review experimental evidence for the existence of both intra-tumor clonal heterogeneity as well as frequent evolutionary divergence between primary tumors and metastatic outgrowths. Furthermore, we discuss potential biological and clinical implications of intra-tumor clonal heterogeneity.

PMID:
19931353
PMCID:
PMC2814927
DOI:
10.1016/j.bbcan.2009.11.002
[Indexed for MEDLINE]
Free PMC Article

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