TY  - JOUR
A1  - Porter, Vanessa L.
A1  - Ng, Michelle
A1  - O'Neill, Kieran
A1  - MacLennan, Signe
A1  - Corbett, Richard D.
A1  - Culibrk, Luka
A1  - Hamadeh, Zeid
A1  - Iden, Marissa
A1  - Schmidt, Rachel
A1  - Tsaih, Shirng-Wern
A1  - Nakisige, Carolyn
A1  - Origa, Martin
A1  - Orem, Jackson
A1  - Chang, Glenn
A1  - Fan, Jeremy
A1  - Nip, Ka Ming
A1  - Akbari, Vahid
A1  - Chan, Simon K.
A1  - Hopkins, James
A1  - Moore, Richard A.
A1  - Chuah, Eric
A1  - Mungall, Karen L.
A1  - Mungall, Andrew J.
A1  - Birol, Inanc
A1  - Jones, Steven J.M.
A1  - Rader, Janet S.
A1  - Marra, Marco A.
T1  - Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation
Y1  - 2025/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 653 
EP  - 670 
DO  - 10.1101/gr.279041.124 
VL  - 35 
IS  - 4 
UR  - http://genome.cshlp.org/content/35/4/653.abstract 
N2  - Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer. To resolve genome dysregulation associated with HPV integration, we performed Oxford Nanopore Technologies long-read sequencing on 72 cervical cancer genomes from a Ugandan data set that was previously characterized using short-read sequencing. We find recurrent structural rearrangement patterns at HPV integration events, which we categorize as del(etion)-like, dup(lication)-like, translocation, multi-breakpoint, or repeat region integrations. Integrations involving amplified HPV–human concatemers, particularly multi-breakpoint events, frequently harbor heterogeneous forms and copy numbers of the viral genome. Transcriptionally active integrants are characterized by unmethylated regions in both the viral and human genomes downstream from the viral transcription start site, resulting in HPV–human fusion transcripts. In contrast, integrants without evidence of expression lack consistent methylation patterns. Furthermore, whereas transcriptional dysregulation is limited to genes within 200 kb of an HPV integrant, dysregulation of the human epigenome in the form of allelic differentially methylated regions affects megabase expanses of the genome, irrespective of the integrant's transcriptional status. By elucidating the structural, epigenetic, and allele-specific impacts of HPV integration, we provide insight into the role of integrated HPV in cervical cancer. 
ER  -