Paper - Review

DOI: 10.1038/nature13385

Abstract

Adenocarcinoma of the lung
→ is the leading cause of cancer death ← worldwide

❗: Molecular profiling of 230 resected lung adenocarcinoma
← using 1⃣ mRNA 2⃣ microRNA 3⃣ DNA sequencing
← integrated with 1⃣ copy number 2⃣ methylation 3⃣ proteomic analyses

∴ High rates of somatic mutations

Eighteen genes
→ were statistically significantly mutated
← e.g. 1⃣ RIT1 activating mutations 2⃣ newly described loss-of-function MGA mutations
← which are mutually exclusive ← with focal MYC amplification

EGFR mutations
→ were more frequent ← in female patients
Mutations in RBM10
→ were more common ← in males

Aberration ← in 1⃣ NF1 2⃣ MET 3⃣ ERBB2 4⃣ RIT1
→ occurred ← in 13% of cases
→ were enriched ← in sample otherwise lacking an activated oncogene
∴ A driver role → for these events in certain tumors

DNA & mRNA sequence
← from the same tumor
→ highlighted splicing alterations
← driven by somatic genomic changes
← e.g. exon 14 skipping ← in MET mRNA in 4% of cases

MAPK & PI(3)K pathway activity
← when measured at the protein level
→ was explained
← by known mutations ← in only a fractions of cases
∴ Additional & unexplained mechanisms of (pathway activation)

Establish a foundation
→ for 1⃣ classification 2⃣ further investigation
← of lung adenocarcinoma molecular pathogenesis

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