Intratumoral heterogeneity and clonal evolution induced by HPV integration

Akagi, Keiko, Symer, David E, Mahmoud, Medhat, Jiang, Bo, Goodwin, Sara, Wangsa, Darawalee, Li, Zhengke, Xiao, Weihong, Dunn, Joe Dan, Ried, Thomas, Coombes, Kevin R, Sedlazeck, Fritz J, Gillison, Maura L (January 2023) Intratumoral heterogeneity and clonal evolution induced by HPV integration. Cancer Discovery. ISSN 2159-8274 (Public Dataset)

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Abstract

The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer. Unique breakpoints shared across structural variants facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that virus and virus-host concatemers are unstable and, upon insertion into and excision from chromosomes, facilitate capture, amplification, and recombination of host DNA and chromosomal rearrangements. Evidence of heterocateny was detected in extrachromosomal and intrachromosomal DNA. These findings indicate that heterocateny is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intratumoral heterogeneity and clonal evolution.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms diseases & disorders > viral diseases diseases & disorders > viral diseases > human papillomavirus bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > insertion/deletion
CSHL Authors:	Goodwin, Sara
Communities:	CSHL Cancer Center Program CSHL Cancer Center Shared Resources > Sequencing Technology & Analysis Service CSHL labs > McCombie lab CSHL labs > Goodwin lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	30 January 2023
Date Deposited:	10 Feb 2023 20:57
Last Modified:	20 Jun 2024 17:54
PMCID:	PMC10070172
Dataset ID:	EGAD00001009630 EGAD00001009631 EGAD00001009632 dbGaP: phs000640
URI:	https://repository.cshl.edu/id/eprint/40840

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