@article{10902/9726,
year = {2014},
url = {http://hdl.handle.net/10902/9726},
abstract = {Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.},
publisher = {Science. 2014 Oct 10;346(6206):251-6},
title = {Spatial and temporal diversity in genomic instability processes defines lung cancer evolution},
author = {Bruin, Elza C de and McGranahan, Nicholas and Mitter, Richard and Salm, Max and Wedge, David C and Yates, Lucy and Jamal-Hanjani, Mariam and Horswell, Stuart and Gerlinger, Marco and Varela Egocheaga, Ignacio and Jones, David and Marshall, John and Voet, Thierry and Loo, Peter van and Rassl, Doris M and Rintoul, Robert C and Janes, Sam M and Lee, Siow-Ming and Foster, Martin and Ahmad, Tanya and Lawrence, David and Falzon, Mary and Capitanio, Arrigo and Harkins, Timothy T and Lee, Clarence C and Tom, Warrem and Teefe, Enok and Chen, Shann-Ching and Begum, Sharmin and Rabinowitz, Adam and Phillimore, Benjamin and Dene, Bradley Spencer and Stamp, Gordon and Szallasi, Zoltan and Matthews, Nik and Stewart, Aengus and Cambell, Peter and Svanton, Charles},
}