PLoS ONE：首次发现白细胞和癌细胞融合可使癌症扩散

近日，来自耶鲁大学癌症研究中心的研究者同科罗拉多大学的研究者共同研究发现，当白细胞和癌细胞共同融合形成一种遗传杂交体时就会导致人类机体转移性肿瘤的发生，相关研究成果刊登于国际杂志PLoS ONE上，该项研究成果或许可以回答癌细胞为何会从最初的肿瘤发生位点转移到其它远距离的机体组织中去的。

在一个多世纪以前这样的理论首次被提出来用以解释癌症的转移，但是截止到现在这种理论在人类癌症中还没有被证实，因为同一病人细胞间的基因组差异非常明显，为了解决这个问题，文中研究者所研究的对象为黑色素瘤脑转移患者，患者患者接受了其兄弟的骨髓移植，研究者对这种患者机体中的二次恶性肿瘤的基因组DNA进行了深入分析。

研究者在肿瘤细胞中发现了来自患者以及捐献者机体中的标记基因，这就表明白细胞（本实验中来自于捐献者）可以和癌细胞进行融合从而引发肿瘤以及肿瘤扩散。

John Pawelek博士表示，我们的研究结果首次证明了1911年由德国病理学家提出的这条理论，就是当白细胞和癌细胞融合形成一种遗传杂交体时就会使得癌症转移发生，这项研究或许为癌症的新型靶向疗法的开发提供思路，但是科学家需要进行更多的研究来确定这种融合是如何发生的以及其发生的频率，同时也要确定这种融合后形成的遗传杂合体在癌症转移中扮演的角色。相关研究由美国安利公司等机构提供资助。

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A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer  

BackgroundTumor 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.
MethodsWe 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.
ResultsAll 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.
ConclusionsOur 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.




来源：生物谷