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- Title
Phasing analysis of lung cancer genomes using a long read sequencer.
- Authors
Sakamoto, Yoshitaka; Miyake, Shuhei; Oka, Miho; Kanai, Akinori; Kawai, Yosuke; Nagasawa, Satoi; Shiraishi, Yuichi; Tokunaga, Katsushi; Kohno, Takashi; Seki, Masahide; Suzuki, Yutaka; Suzuki, Ayako
- Abstract
Chromosomal backgrounds of cancerous mutations still remain elusive. Here, we conduct the phasing analysis of non-small cell lung cancer specimens of 20 Japanese patients. By the combinatory use of short and long read sequencing data, we obtain long phased blocks of 834 kb in N50 length with >99% concordance rate. By analyzing the obtained phasing information, we reveal that several cancer genomes harbor regions in which mutations are unevenly distributed to either of two haplotypes. Large-scale chromosomal rearrangement events, which resemble chromothripsis events but have smaller scales, occur on only one chromosome, and these events account for the observed biased distributions. Interestingly, the events are characteristic of EGFR mutation-positive lung adenocarcinomas. Further integration of long read epigenomic and transcriptomic data reveal that haploid chromosomes are not always at equivalent transcriptomic/epigenomic conditions. Distinct chromosomal backgrounds are responsible for later cancerous aberrations in a haplotype-specific manner. Long-read sequencing technologies are useful for the multifaceted task of characterising somatic mutations, including structural variants, in cancers. Here, the authors combine short and long read sequencing for the phasing analysis, which enables them to resolve the chromosomal backgrounds of somatic mutations in Japanese non-small cell lung cancers.
- Subjects
HAPLOTYPES; SOMATIC mutation; NON-small-cell lung carcinoma; LUNG cancer; GENOMES; CHROMOSOMAL rearrangement
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31133-6