A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis.
BACKGROUND
Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma.


METHODS
Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML), developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes.


RESULTS
DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor.


CONCLUSIONS
The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease.
Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, CO, United States of America.|Denver Police Crime Lab-Forensics and Evidence Division, Denver, Colorado, United States of America.
Greggory S
GS
LaBerge
Denver Police Crime Lab-Forensics and Evidence Division, Denver, Colorado, United States of America.
Eric
E
Duvall
Department of Pathology, University of Colorado AMC, Denver, Colorado, United States of America.
Zachary
Z
Grasmick
Department of Internal Medicine Section of Medical Oncology and the Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, United States of America.
Kay
K
Haedicke
Department of Dermatology and The Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, United States of America.
John
J
Pawelek
D015415:Biomarkers; D016026:Bone Marrow Transplantation; D015894:Genome, Human; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009418:S100 Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000235:genetics*
D015415:Biomarkers; D009418:S100 Proteins