TCGA Lung Adenocarcinoma (LUAD)

Overview

Multi-platform molecular characterization of 230 resected, treatment-naive lung adenocarcinomas by The Cancer Genome Atlas (TCGA) Research Network, combined with 182 previously published cases (n=412 for driver discovery). The study identified 18 significantly mutated genes, nominated novel drivers including RIT1 and MGA, and defined three transcriptional subtypes (TRU, PI, PP). The fraction of LUAD cases with a defined RTK/RAS/RAF activating event was raised from 62% to 76%.

Composition

  • Cancer type: lung adenocarcinoma (LUAD)
  • 230 primary, treatment-naive resected tumors with matched normal tissue; 81% former/current smokers
  • Median follow-up 19 months; 163 alive at last follow-up
  • Statistical pool for driver discovery: n=412 (TCGA n=230 + prior published n=182)
  • Low-pass WGS on n=93 tumor/germline pairs (average 36 gene–gene/inter-gene rearrangements; chromothripsis 6%)

Assays / panels (linked)

Papers using this cohort

  • PMID:25079552 — TCGA Research Network 2014, comprehensive molecular profiling of lung adenocarcinoma
  • PMID:27158780 — Campbell et al. 2016, Nature Genetics: 227 TCGA LUAD cases incorporated into the integrated 1,144-NSCLC exome cohort nsclc_tcga_broad_2016.
  • PMID:28336552 — Jordan et al. 2017, Cancer Discovery: TCGA LUAD used as a retrospective treatment-naïve comparator cohort to benchmark genomic frequencies observed in the prospective MSK-IMPACT lung_msk_2017 cohort.

Notable findings derived from this cohort

  • Mean somatic mutation rate 8.87 mutations/Mb (median 5.78); 18 significantly mutated genes identified by MutSig2CV across n=412 tumors PMID:25079552
  • RIT1 activating mutations (2%, Q79-residue cluster) and NF1 loss-of-function mutations (11%) nominated as novel RTK/RAS/RAF drivers; with focal MET and ERBB2 amplifications, 76% of LUAD now carry a defined RTK/RAS/RAF event (up from 62%) PMID:25079552
  • MGA loss-of-function mutations (8%) are mutually exclusive with focal MYC amplification (P=0.04), revealing a novel MYC-pathway activation mechanism PMID:25079552
  • MET exon 14 skipping in 4% (10/230); U2AF1 S34F mutations drive 129 alternative splicing events including CTNNB1 PMID:25079552
  • Three transcriptional subtypes defined: TRU (terminal respiratory unit, EGFR/fusion-enriched, favorable prognosis), PI (proximal-inflammatory, NF1+TP53), PP (proximal-proliferative, KRAS+STK11) PMID:25079552
  • CIMP-H methylation cluster shows hypermethylation of WNT pathway genes and CDKN2A; MYC overexpression associated with CIMP-H (P=0.003) PMID:25079552
  • 227 cases from this cohort were merged into the integrated nsclc_tcga_broad_2016 Pan-Lung analysis (660 ADC + 484 SqCC); this larger sample identified additional SMGs (PPP3CA, DOT1L, KLF5) and raised the proportion of ADC with a defined RTK/Ras/Raf driver to 76%. PMID:27158780
  • Used as treatment-naïve comparator for the MSK-IMPACT lung_msk_2017 prospective cohort: EGFR activating mutations enriched in MSK cohort (27% vs. 11%, p<0.001); EGFR T790M 5.5% vs. 0.4% (p<0.001) in TCGA; NF1 truncating/deletion lower in MSK (2% vs. 8.3%, p<0.001); BRAF mutations lower (3.6% vs. 7%, p=0.042), reflecting referral and treatment-experience bias. PMID:28336552

Sources

  • cBioPortal studyId: luad_tcga_pub
  • TCGA Data Portal
  • PMID:28336552

This page was processed by entity-page-writer on 2026-05-15.