Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Teixeira VH,Pipinikas CP,Pennycuick A,Lee-Six H,Chandrasekharan D,Beane J,Morris TJ,Karpathakis A,Feber A,Breeze CE,Ntolios P,Hynds RE,Falzon M,Capitanio A,Carroll B,Durrenberger PF,Hardavella G,Brown JM,Lynch AG,Fa

doi

10.1038/s41591-018-0323-0

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

517-525

issue

3

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-018-0323-0

journal_volume

25

pub_type

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