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Long-read Sequencing Identifies Novel Structural Variations in Colorectal Cancer

Luming Xu, Xingyue Wang, Xiaohuan Lu, Fan Liang, Zhibo Liu, Hongyan Zhang, Xiaoqiong Li, ShaoBo Tian, Lin Wang, Zheng Wang.

Structural variations (SVs) are a key type of cancer genomic alterations, contributing to oncogenesis and progression of many cancers, including colorectal cancer (CRC). However, SVs in CRC remain difficult to be reliably detected due to limited SV-detection capacity of the commonly used short-read sequencing. This study investigated the somatic SVs in 21 pairs of CRC samples by Nanopore whole-genome long-read sequencing.

Colorectal cancer (CRC) is the third most common malignancy with over 1.8 million new cases and 0.86 million deaths worldwide in 2018. The development and progression of CRC are largely attributed to genetic alterations, such as structural variations (SVs), single nucleotide variations (SNVs), and epigenetic changes. Among these genetic alterations, the SVs that affect gene expression and function via gene amplification or deletion, gene structure disruption, and gene fusion, are prevalent in CRC  and have been examined in several studies by copy number variation (CNV) arrays and short-read sequencing.

Materials and Methods:

Ethics statement
This study was conducted according to the Helsinki human subject doctrine and was approved by the Huazhong University of Science and Technology review board and Ethics Committee (IORG No. IORG0003571, 2020-S197), written consents to participate was acquired from all the patients.
Sample collection and Oxford nanopore sequencing
21 pairs of tumor samples and matched para-carcinoma samples were obtained from the surgically removed tumor tissues and adjacent intestinal tissues (>6 cm from tumor tissues) of CRC patients in Wuhan Union Hospital, and stored at -80°C.

Structural variations are deemed as oncogenic organizers that alter expression and function of oncogenes or tumor suppressors. However, due to the short read length caused ambiguous alignment, commonly used short-read sequencing strategies are ineffective in breakpoints phasing, and complex or long SVs detection and reconstruction Yet, large amount of hidden structural variations in human genomes need to be further identified.

Citation: Xu L, Wang X, Lu X, Liang F, Liu Z, Zhang H, et al. (2023) Long-read sequencing identifies novel structural variations in colorectal cancer. PLoS Genet 19(2): e1010514.

Editor: Richarda de Voer, Radboudumc, NETHERLANDS

Received: December 12, 2021; Accepted: November 8, 2022; Published: February 22, 2023.

Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The sequence data were deposited in the Genome Sequence Archive (GSA) in the China National Center for Bioinformation (CNCB), under accession number HRA002638, that are publicly accessible (

Funding: This work was supported by the National Natural Science Foundation of China (81773104, 81773263 to LW and 81873931, 81974382 to ZW), the Joint Fund of Ministry of Education for Equipment Pre-research (6141A02022626 to LW), the Major Scientific and Technological Innovation Projects in Hubei Province (2018ACA136 to ZW), the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of HUST (to ZW), the Academic Doctor Supporting Program of Tongji Medical College, HUST (to ZW), and Health Commission of Hubei Province scientific research project (WJ2019M155 to ZW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors declare that they have no competing interests.

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