Cell Fusion Connects Oncogenesis with Tumor Evolution

Xiaofeng Zhou, Kevin Merchak, Woojin Lee, Joseph P. Grande, Marilia Cascalho, Jeffrey L. Platt

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Abstract Cell fusion likely drives tumor evolution by undermining chromosomal and DNA stability and/or by generating phenotypic diversity; however, whether a cell fusion event can initiate malignancy and direct tumor evolution is unknown. We report that a fusion event involving normal, nontransformed, cytogenetically stable epithelial cells can initiate chromosomal instability, DNA damage, cell transformation, and malignancy. Clonal analysis of fused cells reveals that the karyotypic and phenotypic potential of tumors formed by cell fusion is established immediately or within a few cell divisions after the fusion event, without further ongoing genetic and phenotypic plasticity, and that subsequent evolution of such tumors reflects selection from the initial diverse population rather than ongoing plasticity of the progeny. Thus, one cell fusion event can both initiate malignancy and fuel evolution of the tumor that ensues.

Original languageEnglish (US)
Article number2035
Pages (from-to)2049-2060
Number of pages12
JournalAmerican Journal of Pathology
Volume185
Issue number7
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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