Lung Adenocarcinoma Met Organotropism (MSK, Cancer Cell 2023)

Overview

Large MSK cohort of lung adenocarcinoma primaries and metastases profiled with MSK-IMPACT (and a WES subcohort) to identify clinicopathologic and genomic features linked to metastasis, metastatic burden, organotropism, and metastasis-free survival PMID:37084736.

Composition

  • 2,532 primary and metastatic LUAD specimens from 2,309 patients PMID:37084736.
  • Metastatic sites profiled: adrenal gland, bone, CNS, liver/biliary, lung, lymph node, and pleura PMID:37084736.

Assays / panels (linked)

Papers using this cohort

  • PMID:37084736 — Lengel et al., Genomic Mapping of Metastatic Organotropism in Lung Adenocarcinoma.

Notable findings derived from this cohort

  • Ever-metastatic primaries had higher TMB, chromosomal instability, and fraction of genome doubled than never-metastatic primaries; APOBEC SBS2/SBS13 more prevalent in metastases (18% vs 8%, p=0.012), particularly in liver lesions PMID:37084736.
  • Inactivation of TP53, SMARCA4, and CDKN2A correlated with site-specific shorter time to metastasis; SMARCA4 strongly enriched in bone metastases (OR=6.47; time to bone met OR=2.79, p<0.001) PMID:37084736.
  • EGFR activating mutations enriched at adrenal metastases (133/202, 66%); KRAS G12C elevated in primaries that metastasized to liver (21%) vs matched liver metastases (6%, p<0.001) PMID:37084736.
  • Only ~4% of metastases harbored therapeutically actionable alterations undetected in their matched primaries PMID:37084736.

Sources

  • cBioPortal study luad_mskcc_2023_met_organotropism PMID:37084736.

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