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bioRxiv · 10.1101/209718

Nanopore Sequencing Reveals High-Resolution Structural Variation in the Cancer Genome

Gong, L.·Wong, C.-H.·Cheng, W.-C.·Tjong, H.·Menghi, F.·Ngan, C. Y.·Liu, E. T.·Wei, C.-L.
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Abstract

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.

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Gong, L., Wong, C.-H., Cheng, W.-C., Tjong, H., Menghi, F., Ngan, C. Y., Liu, E. T., Wei, C.-L.. 2017-10-26. Nanopore Sequencing Reveals High-Resolution Structural Variation in the Cancer Genome. https://doi.org/10.1101/209718

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