title: A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer.
abstract: Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically.
  
  
  
  We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes.
  
  
  
  All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event.
  
  
  
  Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome.
authors.affiliation: Deptartment of Dermatology, Yale School of Medicine, New Haven, Connecticut, United States of America ; The Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Rossitza
authors.initials: R
authors.lastname: Lazova
authors.forename: Greggory S
authors.initials: GS
authors.lastname: Laberge
authors.forename: Eric
authors.initials: E
authors.lastname: Duvall
authors.forename: Nicole
authors.initials: N
authors.lastname: Spoelstra
authors.forename: Vincent
authors.initials: V
authors.lastname: Klump
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
authors.forename: Dennis
authors.initials: D
authors.lastname: Cooper
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Chang
authors.forename: John M
authors.initials: JM
authors.lastname: Pawelek
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary*; D002459:Cell Fusion; D053803:Forensic Genetics / Q000379:methods; D006801:Humans; D016393:Lymphoma, B-Cell / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000473:pathology*; D020080:Tandem Repeat Sequences; D014019:Tissue Donors