Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.
Adult
Aged
Aged, 80 and over
Carcinogenesis
/ genetics
Carcinoma in Situ
/ genetics
Carcinoma, Squamous Cell
/ genetics
Chromosomal Instability
/ genetics
Cohort Studies
DNA Copy Number Variations
DNA Methylation
/ genetics
Disease Progression
Epigenomics
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics
Humans
Longitudinal Studies
Lung Neoplasms
/ genetics
Male
Middle Aged
Mutation
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
05
09
2018
accepted:
05
12
2018
pubmed:
22
1
2019
medline:
14
5
2019
entrez:
22
1
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30664780
doi: 10.1038/s41591-018-0323-0
pii: 10.1038/s41591-018-0323-0
pmc: PMC7614970
mid: EMS185036
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-525Subventions
Organisme : Wellcome Trust
ID : 211179/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 209199/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211179
Pays : United Kingdom
Organisme : Medical Research Council
ID : G108/596
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
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