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Review
. 2020 Jan;65(1):3-10.
doi: 10.1038/s10038-019-0658-5. Epub 2019 Sep 2.

A new era of long-read sequencing for cancer genomics

Yoshitaka Sakamoto  1 , Sarun Sereewattanawoot  1 , Ayako Suzuki  2
Affiliations
Review

A new era of long-read sequencing for cancer genomics

Yoshitaka Sakamoto et al. J Hum Genet. 2020 Jan.

Abstract

Cancer is a disease largely caused by genomic aberrations. Utilizing many rapidly emerging sequencing technologies, researchers have studied cancer genomes to understand the molecular statuses of cancer cells and to reveal their vulnerabilities, such as driver mutations or gene expression VSports手机版. Long-read technologies enable us to identify and characterize novel types of cancerous mutations, including complicated structural variants in haplotype resolution. In this review, we introduce three representative platforms for long-read sequencing and research trends of cancer genomics with long-read data. Further, we describe that aberrant transcriptome and epigenome statuses, namely, fusion transcripts, as well as aberrant transcript isoforms and the phase information of DNA methylation, are able to be elucidated by long-read sequencers. Long-read sequencing may shed light on novel types of aberrations in cancer genomics that are being missed by conventional short-read sequencing analyses. .

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VSports手机版 - Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Phasing of the allelic relationships between noncoding regulatory regions and exonic regions. a, b An example of phasing by both physical (a) and synthetic (b) long-read technologies. The lines show an allelic relationship of multiple single- nucleotide variants (SNVs) of the SEMA6A gene in the H1975 cell line (previously reported in Sereewattanawoot et al. [21]). Each SNV is represented in a circle. c The scheme for identification of regulatory mutations affecting transcription and gene expression by phasing analysis [21]. Heterozygous regulatory mutations are associated with exonic variations in allele resolution using linked-read sequencing (left). The phasing results are validated by physical long reads. Allelic transcription and expression are also considered to evaluate the impact on regulatory mutations (right). The RNA-seq and ChIP-seq data are used to measure the transcription and expression statuses in allele level
Fig. 2
Fig. 2
Structural variants in lung cancers identified by PromethION. a Five representative types of structural variants in cancer genomes. Ref.: Reference sequences. b The workflow of direct, long-read whole-genome sequencing analysis by PromethION [10]. Intact high-molecular-weight genomic DNA is extracted from fresh or frozen cells. For the construction of sequencing libraries of PromethION, DNA repair, end-prep, and adaptor ligations are conducted according to the manufacturer’s protocols. Sequencing starts after the library is loaded to the flow cell. Base calling is performed to obtain the sequencing read data, because the data are first provided in the fast5 file format. After getting the fastq files, the reads are mapped to the reference genome and/or assembled, and various analyses are conducted, such as SNV/SV calling, methylated base calling, phasing analysis, and visualization by genome viewers
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