A model for HPV superspreading revealed by long-read sequencing of a rare cervical cancer cell line with episomal and integrated HPV16

Nicole Rossi & Michael Dean

Nicole Rossi & Michael Dean, National Cancer Institute, USA

Abstract

Human papillomaviruses (HPV) are a DNA virus replicating as an episome, but often integrates into the tumor genome. We previously documented large HPV concatemers and a superspreading event. We now characterized a cell line with episomal and integrated sequences. Long-read whole genome sequencing revealed concatemers of unintegrated, episomal HPV sequences. To sequence circular HPV molecules, we built libraries using transposase insertion of sequencing adaptors and confirmed the presence of mixed genome concatemers of over 70 kb. Therefore, HPV superspreading may be initiated by amplifying extrachromosomal DNA into large concatemers that integrate into multiple locations in the tumor genome.

Bio

Ms. Nicole Marie Rossi is a Post-Bac fellow in the Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics at the National Cancer Institute, NCI in Rockville, Maryland, USA. She earned her Honors Bachelor of Science Degree in biological sciences from the University of Delaware. As an undergraduate, she worked in Dr. Melinda K Duncan’s lab, studying the role of Lactase-Like (LCTL) gene in lens cell homeostasis and cataract formation.

Dr. Michael Dean is a senior investigator in the Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics at the National Cancer Institute, NCI in Rockville, Maryland, USA. Dr. Dean is interested in inherited (germline) genetic variation, somatic mutations in tumors, and their effects on cancer risk, progression, and response to therapy. The lab has a major focus on human papillomavirus (HPV) and cervical cancer, and cancer health disparities in the U.S. and in Latin America.