Evolution of transmissible cancers and genetics of host resistance

摘要： 癌症不是单一事件。它随着繁殖不断进化，在宿主中传播，并躲避其宿主。 宿主的基本识别机制。我们鉴定了一种逆转录转座子 Steamer，在白血病样细胞中扩增 软壳蛤疾病。通过研究 Steamer 逆转录转座子、mtDNA 的整合位点 SNPs和多态性微卫星，我发现这种疾病是通过水平传播的 白血病细胞本身，作为一种传染性癌症，我们发现这是一种广泛传播的疾病 多双壳类的现象。基于我在博士的指导下进行的初步调查。 哥伦比亚大学的斯蒂芬·戈夫（Stephen Goff），我提议研究传染性癌症的演变以及 逆转录因子 Steamer 在疾病发展中的作用以及支原体传播机制。 沙粒属白血病和宿主耐药性的发展。这项研究将建立在我之前的培训基础上 当我过渡到独立学术研究职位时，我将逆转录病毒学和癌症生物学 开发这种癌症系统作为白血病的独特模型。这将分三个独立完成，但是 相互关联的目标：（1）研究驱动癌症进化的突变和选择压力 包括Steamer逆转录转座子的作用，（2）确定癌细胞的途径和机制 (3) 确定癌细胞植入/排斥的宿主遗传决定因素。这种独特的 无脊椎动物癌症模型将使我们能够更多地了解癌症的进化以及逆转录因子在癌症中的作用 癌症，并研究白血病的获得和自我/非自我识别的基本机制。

SUMMARY: Cancer is not a single event. It continues to evolve as is multiplies, spreads through its host, and evades its host’s basic mechanisms of recognition. We identified a retrotransposon, Steamer, amplified in a leukemia-like disease in soft-shell clams. Through investigation of integration sites of the Steamer retrotransposon, mtDNA SNPs, and polymorphic microsatellites, I discovered that the disease is spread by horizontal transmission of leukemic cells themselves, acting as a contagious cancer, and we have found that this is a widespread phenomenon in multiple bivalves. Based on my preliminary investigations while under the mentorship of Dr. Stephen Goff at Columbia University, I propose to investigate the evolution of transmissible cancers and the role of the retroelement, Steamer, in development of the disease as well as the mechanism of transmission of M. arenaria leukemia and the development of host resistance. This research will build on my previous training in retrovirology and cancer biology as I transition into independent academic research position where I will develop this cancer system as a unique model of leukemia. This will be done in three independent, but interconnected aims: (1) Investigate the mutations and selective pressures which drive cancer evolution including the role of the Steamer retrotransposon, (2) determine the route and mechanism of cancer cell transmission, and (3) identify the host genetic determinants of cancer cell engraftment/rejection. This unique invertebrate cancer model will allow us to learn more about cancer evolution and the role of retroelements in cancer, and to investigate leukemia acquisition and fundamental mechanisms of self/nonself recognition.