Abstract
Epithelial cancers can arise from BM-derived cells (BMCs) in animal models. We studied whether the same phenomenon can occur in humans. Biopsy specimens from carcinomas and healthy adjacent tissues were obtained from three women who had undergone allogeneic BMT from an HLA-matched brother. Complete donor hematopoietic chimerism was verified by cytogenetic analysis, RFLP analysis or by reverse transcription-PCR analysis. Biopsies were studied for the presence of the Y chromosome derived from BM-derived cells by combined FISH and immunohistochemical staining. In our studies, we showed that human epithelial neoplastic and adjacent non-neoplastic tissues incorporate the Y chromosome at low and comparable rates. The lack of enrichment in malignancies argues against the possibility that BM-derived cells represent a direct source of carcinomas, and we suggest that these cells randomly contribute to neoplastic and non-neoplastic epithelial cells. On the basis of the absence of a fusion karyotype, we favor a model in which the differentiation of BM-derived cells is largely determined by the microenvironment encountered.
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Acknowledgements
We thank A Camponovo and M Ghisletta for continuous help. We are especially indebted to K Basler, G Schwank and M Frattini for providing technical support and to J Martinalbo, L Leoncini and M Manz for discussions. We are also grateful to E Passega Sidler and G Hausmann for comments on the manuscript. This work was supported by grants from the Helmut Horten Stiftung and the San Salvatore Foundation.
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Soldini, D., Moreno, E., Martin, V. et al. BM-derived cells randomly contribute to neoplastic and non-neoplastic epithelial tissues at low rates. Bone Marrow Transplant 42, 749–755 (2008). https://doi.org/10.1038/bmt.2008.243
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DOI: https://doi.org/10.1038/bmt.2008.243
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