RT Journal Article
SR Electronic
T1 Nanopore Sequencing Reveals High-Resolution Structural Variation in the Cancer Genome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 209718
DO 10.1101/209718
A1 Liang Gong
A1 Chee-Hong Wong
A1 Wei-Chung Cheng
A1 Harianto Tjong
A1 Francesca Menghi
A1 Chew Yee Ngan
A1 Edison T. Liu
A1 Chia-Lin Wei
YR 2017
UL http://biorxiv.org/content/early/2017/10/26/209718.abstract
AB Acquired genomic structural variants (SVs) are major hallmarks of the cancer genome. Their complexity has been challenging to reconstruct from short-read sequencing data. Here, we exploit the long-read sequencing capability of the nanopore platform using our customized pipeline, Picky, to reveal SVs of diverse architecture in a breast cancer model. From modest sequencing coverage, we identified the full spectrum of SVs with superior specificity and sensitivity relative to short-read analyses and uncovered repetitive DNA as the major source of variation. Examination of the genome-wide breakpoints at nucleotide-resolution uncovered micro-insertions as the common structural features associated with SVs. Breakpoint density across the genome is associated with propensity for inter-chromosomal connectivity and transcriptional regulation. Furthermore, an over-representation of reciprocal translocations from chromosomal double-crossovers was observed through phased SVs. The comprehensive characterization of SVs using the robust long-read sequencing approach in cancer cohorts will facilitate strategies to monitor genome stability during tumor evolution and improve therapeutic intervention.