Paper - Review

DOI: 10.1038/s41591-018-0323-0

Abstract

The molecular alterations
← that occur in cell before cancer is manifest
→ are largely uncharted

Lun carcinoma in situ (CIS) lesions
→ are the pre-invasive precursor → to squamous cell carcinoma

Their future is in equipoise
→ 1⃣ half progressing → to invasive cancer
→ 2⃣ half regression & remaining static

❓: The cellular basis of this clinical observation → is unknown

❗: Profile → 1⃣ genomic 2⃣ transcriptomic 3⃣ 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

Identify → progression-specific methylation
→ changes on a background of widespread heterogeneity
← alongside a strong chromosomal instability signature

Observed 1⃣ mutations 2⃣ copy number changes characteristic of cancer
Chart their emergence
∴ offering a window → into early carcinogenesis

This new understanding of cancer precursor biology
→ will improve early detection
→ reduce over-treatment
→ foster preventative therapies → targeting early clonal event ← in lung caner

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