Occurrence and regression of BK polyomavirus associated carcinoma: a clinical and next-generation sequencing study

doi:10.1042/CS20180443

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	Occurrence and regression of BK polyomavirus associated carcinoma: a clinical and next-generation sequencing study
	Fu, Fangxiang 2; Deng, Wenfeng 3; Yu, Siyuan 4; Liu, Yanna 2; Yu, Lixin 3; Liu, Rumin 3; Lang, Jiping 2; Geng, Dianxiang 5; Geng, Jian 6; Li, Jiangtao 2
刊名	CLINICAL SCIENCE
	2018-08-31
卷号	132 期号:16 页码:1753-1763
ISSN号	0143-5221
DOI	10.1042/CS20180443
英文摘要	Low-level BK polyomavirus (BKPyV) shedding is seen in at least 10% of seropositive immunocompetent adults. Moreover, BKPyV infection is highly prevalent amongst immuno-compromised populations, yet little is known on its relationship with malignancy. We studied a female patient with BKPyV-associated and donor-derived de novo high-grade sarcomatoid urothelial carcinoma developed 8 years after kidney transplantation from a male donor. Through whole-genome sequencing, we discovered integration of genotype IV BKPyV genome into the non-coding RNA (ncRNA) intronic region of human chromosome 18. The two breakpoints in the virus genome were located at the non-coding control region (NCCR) and large T antigen (TAg) coding region, respectively. Nevertheless, the TAg was overexpressed. We, therefore, inferred that the BKPyV was clonally integrated into the human genome in the form of concatemers, facilitating the expression of the TAg. The patient presented with multiorgan metastases, which were reduced in size and number throughout the body after removal of the graft and cessation of immunosuppressants. The few remaining lesions located in the liver were identified, through biopsy to be necrotic tumor tissue with TAg detected; additionally, genomic sequencing of the liver mass found Y chromosome. In conclusion, we propose that integration of the BKPyV genome is closely related to oncogenesis in this patient; while oncogenesis occurred when host immunity was impaired, recovery of the patient's native immunity effectively curbed viral replication and eliminated the metastatic lesions.
资助项目	National Natural Science Foundation of China[81500573] ; Science and Technology Planning Project of Guangzhou[201803010109]
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000443728700003
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/3421]
专题	中国科学院武汉植物园
通讯作者	Miao, Yun
作者单位	1.Harvard Med Sch, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA 2.Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China 3.Southern Med Univ, Nanfang Hosp, Organ Transplant Dept, Guangzhou 510515, Guangdong, Peoples R China 4.Southern Med Univ, Clin Med Sch 2, Guangzhou 510515, Guangdong, Peoples R China 5.Vazyme Biotech Co Ltd, Dept Informat Anal, Nanjing 210000, Jiangsu, Peoples R China 6.Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China 7.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Organ Transplantat, Guangzhou 510080, Guangdong, Peoples R China 8.Wuhan Inst Virol, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Virol, Wuhan, Hubei, Peoples R China 9.Southern Med Univ, Sch Basic Med Sci, Dept Med Genet, Guangzhou 510515, Guangdong, Peoples R China 10.Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
推荐引用方式 GB/T 7714	Fu, Fangxiang,Deng, Wenfeng,Yu, Siyuan,et al. Occurrence and regression of BK polyomavirus associated carcinoma: a clinical and next-generation sequencing study[J]. CLINICAL SCIENCE,2018,132(16):1753-1763.
APA	Fu, Fangxiang.,Deng, Wenfeng.,Yu, Siyuan.,Liu, Yanna.,Yu, Lixin.,...&Miao, Yun.(2018).Occurrence and regression of BK polyomavirus associated carcinoma: a clinical and next-generation sequencing study.CLINICAL SCIENCE,132(16),1753-1763.
MLA	Fu, Fangxiang,et al."Occurrence and regression of BK polyomavirus associated carcinoma: a clinical and next-generation sequencing study".CLINICAL SCIENCE 132.16(2018):1753-1763.