1. Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype.
- Author
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Belloni E, Veronesi G, Rotta L, Volorio S, Sardella D, Bernard L, Pece S, Di Fiore PP, Fumagalli C, Barberis M, Spaggiari L, Pelicci PG, and Riva L
- Subjects
- DNA-Binding Proteins genetics, Exome, Genetic Predisposition to Disease, Humans, Intracellular Signaling Peptides and Proteins genetics, Karyotype, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms pathology, MutL Proteins, MutS Homolog 3 Protein, Neoplasm Proteins genetics, Tomography, X-Ray Computed, Tumor Suppressor Protein p53 genetics, High-Throughput Nucleotide Sequencing methods, Lung Neoplasms genetics, Mutation, Sequence Analysis, DNA methods
- Abstract
The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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