生物谷报道:来自匹兹堡大学癌症研究院(University of Pittsburgh Cancer Institute)分子病毒研究组的研究人员提出了一种寻找人类病毒的新方法:他们发现引起卡波济氏肉瘤(Kaposi’s Sarcoma,生物谷注)的原因是之前未知的一种病毒,这种病毒与另一少见,但是致命的皮肤癌——Merkel细胞癌(merkel cell carcinoma,www.ebiotrade.com)密切相关。这一研究成果公布在上周五(1月18日)出版的Science在线版上。
领导这一研究,文章的通讯作者是癌症研究院KSHV实验室的Patrick S. Moore与Yuan Chang,这两位分子病毒学领域的专家教授是一对夫妻,前者毕业于斯坦福大学,实验室主要兴趣在于研究KSHV与宿主信号途径之间的基础关系。
这一新获得的研究成果花费了他们十年的时间,利用测序技术识别这种MCV病毒(Merkel cell polyomavirus),这也许能提供一种新的癌症治疗及预防措施。
Moore博士表示,“这是第一个发现的与某种特殊类型的人类肿瘤密切相关的多瘤病毒(polyomavirus,www.ebiotrade.com)”——多瘤病毒PY能诱发多个部位或器官发生肉瘤或癌症,因此称为多瘤病毒,“虽然多瘤病毒在癌症发育方面已经研究了多年,但是许多重要证据都表明这些病毒并不会引发人类癌症。”
Merkel细胞癌(MCC)是原发于皮肤的一种高度恶性肿瘤,1972年Toker首先描述并用”梁状癌”命名,因其肿瘤细胞质内有神经内分泌颗粒出现,也被称作原发于皮肤的神经内分泌癌。主要发生于老年人的头颈部及四肢,具有独特的超微结构改变和免疫组化染色特征。在过去的20年间,MCC增长了三倍,每年出现1500个病例,这种癌症主要发生在免疫系统受到AIDS,或者移植相关免疫抑制药物破坏的个体身上,一半患有MCC的病人只能存活至多9个月,三分之二的病人在5年内会死亡。
“如果我们的这些研究成果得到进一步证实,我们就能了解这种新病毒是如何导致这一高致死率的癌症的发生,而且重要的是,利用这一模式,我们能了解癌症发生,及其癌症发生过程中的细胞途径的变化”,Moore博士说。
生物谷推荐原始出处:
Published Online January 17, 2008
Science DOI: 10.1126/science.1152586
Submitted on November 5, 2007
Accepted on January 8, 2008
Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma
Huichen Feng 1, Masahiro Shuda 1, Yuan Chang 1*, Patrick S. Moore 1*
1 Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Ave, Suite 1.8, Pittsburgh, PA 15213, USA.
* To whom correspondence should be addressed.
Yuan Chang , E-mail: yc70@pitt.edu
Patrick S. Moore , E-mail: psm9@pitt.edu
These authors contributed equally to this work.
Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction (DTS) and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to discovery and sequence analysis of the 5387-base-pair genome of a new polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but in only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of 8 MCV-positive MCCs, viral DNA was integrated within the tumor genome in a pattern suggesting that MCV infection/integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.