Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability

被引：349

作者：

Akagi, Keiko ^{[1
,2
,3
]}

Li, Jingfeng ^{[1
,2
,3
]}

Broutian, Tatevik R. ^{[2
,4
]}

Padilla-Nash, Hesed ^{[5
]}

Xiao, Weihong ^{[2
,4
]}

Jiang, Bo ^{[2
,4
]}

Rocco, James W. ^{[6
,7
,8
]}

Teknos, Theodoros N. ^{[9
]}

Kumar, Bhavna ^{[9
]}

Wangsa, Danny ^{[5
]}

He, Dandan ^{[1
,2
,3
]}

Ried, Thomas ^{[5
]}

Symer, David E. ^{[1
,2
,3
,4
,10
]}

Gillison, Maura L. ^{[2
,4
]}

机构：

[1] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA

[2] Ohio State Univ, Ctr Comprehens Canc, Viral Oncol Program, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[4] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA

[5] NCI, Canc Genom Sect, Ctr Canc Res, Bethesda, MD 20814 USA

[6] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[8] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA

[9] Ohio State Univ, Wexner Med Ctr, Dept Otolaryngol Head & Neck Surg, Columbus, OH 43210 USA

[10] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA

来源：

GENOME RESEARCH | 2014年 / 24卷 / 02期

关键词：

HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMA; HEPATITIS-B-VIRUS; STRUCTURAL ALTERATIONS; GENETIC INSTABILITY; CERVICAL-CARCINOMA; DNA; HEAD; REPLICATION; ESTABLISHMENT;

D O I：

10.1101/gr.164806.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of "looping" by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.

引用

页码：185 / 199

页数：15

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