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.
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.
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DOI：
10.1371/journal.pone.0168581
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Pawelek J
中科院分区：
文献类型：
--
作者：
LaBerge GS;Duvall E;Grasmick Z;Haedicke K;Pawelek J
转移性疾病是癌症死亡的主要原因，但其潜在机制尚未完全了解。巨噬细胞-癌细胞融合作为转移的原因是由德国病理学家Otto Aichel教授在世纪前提出的。从那时起，这一理论已经在许多动物研究中得到证实，最近在转移性黑色素瘤患者中得到证实。在这里，我们分析了一名51岁男子的肿瘤DNA，他在接受其兄弟的同种异体BMT治疗慢性粒细胞白血病（CML）8年后，在上背部发展为结节性恶性黑色素瘤并扩散到腋窝前哨淋巴结。我们使用激光显微切割来分离不含白细胞的FFPE肿瘤细胞。使用法医短串联重复序列（STR）长度多态性对他们进行基因分型，以区分供体和患者基因组。分析肿瘤和移植前血液淋巴细胞DNA中15个常染色体STR基因座和性染色体上的供体和患者等位基因。原发性黑色素瘤和淋巴结转移瘤的DNA分析显示，每个STR基因座的等位基因与患者和供体一致。这些样品之间的剂量不同，指示来自患者和供体的基因组DNA的相对量。证据支持供体和患者细胞之间的融合和杂交作为该患者转移的起始物。这种现象现在已经在第二个病例中看到，表明融合可能在黑色素瘤和其他实体瘤转移中发挥重要作用，可能为这种最有问题的疾病带来新的治疗途径。
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. 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. 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. 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.