Long-read sequencing of cervical cancer cell lines reveals digestion of DNA ends during Breakage-Fusion-Bridge events in cancer
)
Cervical cancer ranks fourth in cancer prevalence and mortality worldwide, with significant disparities in incidence and mortality associated with poverty. Currently there are no targeted therapeutic approaches for treatment. To provide improved models for cervical cancer therapeutics we characterized 22 cell lines using long-read DNA and RNA sequencing. Cervical cancer cell lines have several recurrent chromosomal alterations, and structural variation analysis of long-read sequences revealed telomeric deletions associated with DNA inversions consistent with breakage-fusion-bridge cycles. Analysis of the DNA sequences at the inversion site revealed staggered ends consistent with exonuclease deletion of the ends after breakage and before fusion (Breakage- Digestion-Fusion-Bridge, BDFB). Events involved the insertion of sequences from another chromosome or local rearrangement, indicating that BFB is complex. The chr11q BFB event, with YAP1/BIRC2/BIRC3 amplification, is more common in cervical cancer than other cancers.