A small cell lung cancer genome reports complex tobacco exposure signatures

By E. Pleasance, P. Stephens, S. O’Meara, D. Mcbride, Alison M. Meynert, David Jones, Meng‐Lay Lin, D. Beare, K. Lau, C. Greenman and 30 more. Nature, 2009

880 citations recorded by the source corpus.

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3–8 of CHD7 in frame, and another two lines carrying PVT1–CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/7d680df02876b889d549c387f019b1e055e84f89

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Citations in the corpus

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Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation (2011, background): “…of the SNP and exome se quencing platforms, this mutation burden is 5–20 times lower than that observed in solid tumor genomes (Jones et al., 2008; Pleasance et al., 2010a; Pleasance et al., 2010b), in multiple 1392 The CLL coding genome | Fabbri et al. protein between the third BIR domain and…”
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