TY  - JOUR
A1  - Sakamoto, Yoshitaka
A1  - Xu, Liu
A1  - Seki, Masahide
A1  - Yokoyama, Toshiyuki T.
A1  - Kasahara, Masahiro
A1  - Kashima, Yukie
A1  - Ohashi, Akihiro
A1  - Shimada, Yoko
A1  - Motoi, Noriko
A1  - Tsuchihara, Katsuya
A1  - Kobayashi, Susumu S.
A1  - Kohno, Takashi
A1  - Shiraishi, Yuichi
A1  - Suzuki, Ayako
A1  - Suzuki, Yutaka
T1  - Long-read sequencing for non-small-cell lung cancer genomes
Y1  - 2020/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1243 
EP  - 1257 
DO  - 10.1101/gr.261941.120 
VL  - 30 
IS  - 9 
UR  - http://genome.cshlp.org/content/30/9/1243.abstract 
N2  - 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. 
ER  -