Low-depth native-molecule whole-genome nanopore-sequencing of lung cancer cell-free DNA samples with EGFR and TP53 co-mutations
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Genetic mutation of the tyrosine kinase EGFR and tumour suppressor TP53 is common in advanced non-small cell lung cancer (NSCLC). Lung cancers with EGFR and TP53 co-mutations are aggressive, are resistant to treatment, and have poor prognoses. Sequencing of cell-free DNA (cfDNA) from blood plasma provides a low intervention alternative to tissue biopsy. Targeted sequencing of cancer cfDNA has emerged as a major diagnostic method but involves specialized lab work. Low-depth native-molecule whole-genome nanopore-sequencing offers a rapid and inexpensive alternative for profiling of cancer cfDNA. We evaluated this strategy with ten normal and ten lung cancer cfDNA samples with EGFR and TP53 co-mutations and assessed somatic copy number alterations (SCNAs), fragment lengths, and differential methylation.