Comprehensive molecular profiling of lung adenocarcinoma¶

One-paragraph summary¶

The Cancer Genome Atlas profiled 230 resected lung adenocarcinomas using exome sequencing, copy number, messenger RNA, microRNA, methylation, and protein measurements. The study reported a mean 8.9 mutations per megabase, 18 significantly mutated genes, recurrent RTK–RAS–RAF pathway activation, and new candidate alterations including activating RIT1 and loss-of-function MGA (PMID 25079552).

Key findings¶

230 surgically resected primary adenocarcinomas.
Multiplatform rather than sequencing-only characterization.
Mean somatic mutation density: 8.9/Mb.
18 significantly mutated genes under the analysis framework.
RTK/RAS/RAF activation was distributed across mutually informative driver events.
Co-alterations and copy-number states showed that a driver does not define the whole tumor.

Limitations¶

Resected tumors underrepresent metastatic and frail populations.
One-time bulk sampling cannot reconstruct later treatment-selected resistance.
Statistical recurrence does not establish drug dependency.
Ancestry and never-smoker representation were limited relative to the global disease.

Why it matters¶

TCGA supplied the reference map from which modern adenocarcinoma testing and pathway hypotheses grew. It also established a lasting caution: frequent alteration, actionable alteration, and validated predictive biomarker are different categories.

Cited by wiki pages¶

Overview
Molecular landscape
Molecular testing
Biomarkers
Systemic therapy