RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2020 
FD September 01 
VO 30 
IS 9 
SP 1243 
OP 1257 
DO 10.1101/gr.261941.120 
UL http://genome.cshlp.org/content/30/9/1243.abstract 
AB 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.