Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions
Vitor H. Teixeira,Christodoulos P. Pipinikas,Adam Pennycuick,Henry Lee-Six,Deepak P. Chandrasekharan,Jennifer Beane,Tiffany Morris,Anna Karpathakis,Andrew Feber,Charles E. Breeze,Paschalis Ntolios,Robert E. Hynds,Robert E. Hynds,Mary Falzon,Arrigo Capitanio,Bernadette Carroll,Pascal F. Durrenberger,Georgia Hardavella,James Brown,Andy G. Lynch,Henry Farmery,Dirk S. Paul,Rachel C. Chambers,Nicholas McGranahan,Neal Navani,Neal Navani,Ricky Thakrar,Ricky Thakrar,Charles Swanton,Stephan Beck,Phillip Jeremy George,Avrum Spira,Avrum Spira,Peter J. Campbell,Christina Thirlwell,Sam M. Janes,Sam M. Janes +36 more
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TLDR
A multi-omics survey of progressive compared to regressive carcinoma in situ lesions provides a molecular map of early lung cancer development and is expected to improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.Abstract:
The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.read more
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Integrative Genomics Viewer
James T. Robinson,Helga Thorvaldsdottir,Wendy Winckler,Mitchell Guttman,Eric S. Lander,Eric S. Lander,Gad Getz,Jill P. Mesirov +7 more
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Journal ArticleDOI
Molecular profiling for precision cancer therapies.
TL;DR: This review summarizes the current and upcoming approaches to implement precision cancer medicine, highlighting the challenges and potential solutions to facilitate the interpretation and to maximize the clinical utility of molecular profiling results.
Journal ArticleDOI
Context is everything: aneuploidy in cancer
Uri Ben-David,Angelika Amon +1 more
TL;DR: The context dependency of aneuploidy in cancer is explained and its clinical potential is discussed, which may have clinical relevance as a prognostic marker and as a potential therapeutic target.
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Tobacco smoking and somatic mutations in human bronchial epithelium
Kenichi Yoshida,Kate H.C. Gowers,Henry Lee-Six,Deepak P. Chandrasekharan,Tim H. H. Coorens,Elizabeth F. Maughan,Kathryn Beal,Andrew Menzies,Fraser R. Millar,Elizabeth Anderson,Sarah E. Clarke,Adam Pennycuick,Ricky Thakrar,Ricky Thakrar,Colin R. Butler,Colin R. Butler,Nobuyuki Kakiuchi,Tomonori Hirano,Robert E. Hynds,Michael R. Stratton,Inigo Martincorena,Sam M. Janes,Sam M. Janes,Peter J. Campbell,Peter J. Campbell +24 more
TL;DR: W Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelia with near-normal cells.
Journal ArticleDOI
Intratumoral heterogeneity in cancer progression and response to immunotherapy.
TL;DR: In this paper, the authors discuss the main sources of intratumoral heterogeneity and its impact on the natural history of the disease, including sensitivity to treatment, as well as delineate potential strategies to target such a detrimental feature of aggressive malignancies.
References
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Journal ArticleDOI
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Journal ArticleDOI
KEGG: Kyoto Encyclopedia of Genes and Genomes
Minoru Kanehisa,Susumu Goto +1 more
TL;DR: The Kyoto Encyclopedia of Genes and Genomes (KEGG) as discussed by the authors is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules.
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limma powers differential expression analyses for RNA-sequencing and microarray studies
Matthew E. Ritchie,Belinda Phipson,Di Wu,Yifang Hu,Charity W. Law,Wei Shi,Gordon K. Smyth,Gordon K. Smyth +7 more
TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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Journal ArticleDOI
Integrative genomics viewer
James T. Robinson,Helga Thorvaldsdottir,Wendy Winckler,Mitchell Guttman,Eric S. Lander,Eric S. Lander,Gad Getz,Jill P. Mesirov +7 more
TL;DR: In this article, the authors present an approach for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
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