Long-read sequencing for non-small-cell lung cancer genomes
Abstract
Here, we report the application of a long-read sequencer, PromethION, for analyzing human cancer genomes. We first conducted whole-genome sequencing on lung cancer cell lines. We found that it is possible to genotype known cancerous mutations, such as point mutations. We also found that long-read sequencing is particularly useful for precisely identifying and characterizing structural aberrations, such as large deletions, gene fusions, and other chromosomal rearrangements. In addition, we identified several medium-sized structural aberrations consisting of complex combinations of local duplications, inversions, and microdeletions. These complex mutations occurred even in key cancer-related genes, such as STK11, NF1, SMARCA4, and PTEN. The biological relevance of those mutations was further revealed by epigenome, transcriptome, and protein analyses of the affected signaling pathways. Such structural aberrations were also found in clinical lung adenocarcinoma specimens. Those structural aberrations were unlikely to be reliably detected by conventional short-read sequencing. Therefore, long-read sequencing may contribute to understanding the molecular etiology of patients for whom causative cancerous mutations remain unknown and therapeutic strategies are elusive.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2020
- Source ID
- 10.1101/gr.261941.120
Entities
People
- Akihiro Ohashi
- Ayako Suzuki
- Katsuya Tsuchihara
- Masahide Seki
- Masahiro Kasahara
- Noriko Motoi
- Susumu S Kobayashi
- Takashi Kohno
- Toshiyuki T. Yokoyama
- Xu Liu
- Yoko Shimada
- Yoshitaka Sakamoto
- Yuichi Shiraishi
- Yukie Kashima
- Yutaka Suzuki
Organizations
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science
- National Cancer Center
- National Institutes of Health
- Taiho Pharmaceutical
- United States Department of Defense