Journal
SCIENCE
Volume 346, Issue 6206, Pages 251-256Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1253462
Keywords
-
Categories
Funding
- Cancer Research UK
- Rosetrees Trust
- UK Medical Research Council
- Spanish Ministerio de Economia y Competitividad
- Cambridge Biomedical Research Centre
- Cancer Research UK Cancer Centre
- European Union [259303]
- Prostate Cancer Foundation
- European Research Council
- Breast Cancer Research Foundation
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Servicio Santander Supercomputacion
- 14M Genomics Ltd
- MRC [G0902275] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL7-Murugaesu] Funding Source: researchfish
- Cancer Research UK [18377, 17786] Funding Source: researchfish
- Medical Research Council [G0902275] Funding Source: researchfish
- National Institute for Health Research [CL-2011-18-001] Funding Source: researchfish
- Rosetrees Trust [M35-F1-CD1] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available