title: Cell Fusion Connects Oncogenesis with Tumor Evolution.
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.
authors.affiliation: Departments of Microbiology and Immunology and Surgery, University of Michigan, Ann Arbor, Michigan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Departments of Microbiology and Immunology and Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kevin
authors.initials: K
authors.lastname: Merchak
authors.affiliation: Departments of Microbiology and Immunology and Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Woojin
authors.initials: W
authors.lastname: Lee
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.affiliation: Departments of Microbiology and Immunology and Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Marilia
authors.initials: M
authors.lastname: Cascalho
authors.affiliation: Departments of Microbiology and Immunology and Surgery, University of Michigan, Ann Arbor, Michigan. Electronic address: plattjl@umich.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Platt
mesh_terms: D000782:Aneuploidy; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002459:Cell Fusion; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D043171:Chromosomal Instability; D002999:Clone Cells / Q000166:cytology / Q000502:physiology; D004249:DNA Damage; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005856:Germ-Free Life; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D059785:Karyotype; D051379:Mice; D016688:Mice, Inbred NOD; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D012692:Serial Passage