Cytogenetic analysis of tumor clonality

Adv Cancer Res. 2011;112:127-49. doi: 10.1016/B978-0-12-387688-1.00005-3.


All or almost all neoplasias subjected to systematic cytogenetic scrutiny have been found to harbor acquired chromosomal aberrations. The paradigm stemming from the study of hematopoietic malignancies and sarcomas is that cancers are of monoclonal origin (i.e., they have developed from a single transformed somatic progenitor) because all the neoplastic parenchyma cells share at least one primary chromosomal abnormality, with subsequent clonal evolution along the lines of Darwinian selection occurring among the various subclones carrying secondary aberrations. When carcinomas began to be studied more extensively by cytogenetic methods, however, sometimes many cytogenetically unrelated clones were found, in seeming contradiction to the monoclonal hypothesis. Also studies of multiple samples from the same patient led to a rethinking of what the cytogenetic evidence really revealed about tumor clonality, both in its early stages and during disease development. The observed cytogenetic heterogeneity in, for example, tumors of the breast and pancreas vastly surpasses that of leukemias, lymphomas, connective tissue tumors, or even most epithelial, including uroepithelial, tumors. Theoretical reasoning as well as the available experimental data we here review show that the clonal evolution of neoplastic cell populations follows either of four principal pathways: (1) initial monoclonality is retained throughout the entire course of the disease with no additional, secondary aberrations accrued as judged by karyotypic appearance; (2) tumorigenesis is monoclonal but additional aberrations develop with time leading to secondary clonal heterogeneity (clonal divergence); (3) polyclonal tumorigenesis exists from the beginning but is followed by an overall reduction in genomic complexity with time (clonal convergence) due to selection among cytogenetically unrelated clones during tumor progression, resulting in secondary oligo- or monoclonality; or (4) polyclonal tumorigenesis with early clonal convergence is followed by later clonal divergence due to the acquisition of additional cytogenetic changes by the clone(s) that survived during the middle phases of tumor progression. Further studies of individual tumor cells are necessary to elicit precise information about the cell-to-cell variability that exists in many, especially epithelial, neoplasms and which holds the key to a more profound understanding of the complex issue of tumor clonality during all stages of cancer development.

Publication types

  • Review

MeSH terms

  • Chromosome Aberrations*
  • Clonal Evolution*
  • Cytogenetic Analysis
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology*