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Updated: Sep 7, 2025
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Published on: November 5, 2019
Phasing analysis of lung cancer genomes using a long read sequencer
Yoshitaka Sakamoto1, Shuhei Miyake1, Miho Oka1,2
1Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Cancer genomes show uneven mutation distribution on chromosome haplotypes. Small-scale rearrangements, characteristic of EGFR-positive lung cancer, drive these biased distributions, revealing distinct chromosomal backgrounds in cancer development.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Understanding the chromosomal basis of cancer mutations is crucial.
- Non-small cell lung cancer (NSCLC) presents complex genomic alterations.
- Haplotype-specific mutation distributions in cancer remain largely unexplored.
Purpose of the Study:
- To investigate the haplotype-specific distribution of mutations in NSCLC.
- To identify chromosomal events contributing to biased mutation patterns.
- To explore the role of chromosomal background in cancer development.
Main Methods:
- Phasing analysis of NSCLC specimens using combined short and long read sequencing.
- Analysis of mutation distribution across haplotypes.
- Integration of long-read epigenomic and transcriptomic data.
Main Results:
- Achieved long phased blocks (>834 kb N50) with high concordance (>99%).
- Identified cancer genomes with uneven mutation distribution biased to specific haplotypes.
- Observed small-scale chromosomal rearrangements, similar to chromothripsis, on single chromosomes, explaining biased distributions.
- Found these events are characteristic of EGFR mutation-positive lung adenocarcinomas.
- Revealed non-equivalent transcriptomic/epigenomic conditions between haploid chromosomes.
Conclusions:
- Distinct chromosomal backgrounds and haplotype-specific aberrations contribute to cancer development.
- Small-scale chromosomal rearrangements play a significant role in shaping cancer genomes.
- EGFR mutation-positive lung adenocarcinomas exhibit characteristic haploid chromosomal events.
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