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Long-read sequencing for non-small-cell lung cancer genomes

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 se...

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Detalles Bibliográficos
Autores principales: Sakamoto, Yoshitaka, Xu, Liu, Seki, Masahide, Yokoyama, Toshiyuki T., Kasahara, Masahiro, Kashima, Yukie, Ohashi, Akihiro, Shimada, Yoko, Motoi, Noriko, Tsuchihara, Katsuya, Kobayashi, Susumu S., Kohno, Takashi, Shiraishi, Yuichi, Suzuki, Ayako, Suzuki, Yutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545141/
https://www.ncbi.nlm.nih.gov/pubmed/32887687
http://dx.doi.org/10.1101/gr.261941.120
Descripción
Sumario: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.