Targeted DNA sequencing of non-small cell lung cancer identifies mutations associated with brain metastases.
Introduction: This study explores the hypothesis that dominant molecular oncogenes in non-small cell lung cancer (NSCLC) are associated with metastatic spread to the brain.
Methods: NSCLC patient groups with no evidence of metastasis, with metastatic disease to a non-CNS site, who developed brain metastasis after diagnosis, and patients with simultaneous diagnosis of NSCLC and metastatic brain lesions were studied using targeted sequencing.
Results: In patients with brain metastasis versus those without, only 2 variants (one each in BCL6 and NOTHC2) were identified that occurred in ≥ 4 NSCLC of patients with brain metastases but ≤ 1 of the NSCLC samples without brain metastases. At the gene level, 20 genes were found to have unique variants in more than 33% of the patients with brain metastases. When analyzed at the patient level, these 20 genes formed the basis of a predictive test to discriminate those with brain metastasis. Further analysis showed that PI3K/AKT signaling is altered in both the primary and metastases of NSCLC patients with brain lesions.
Conclusion: While no single variant was associated with brain metastasis, this study describes a potential gene panel for the identification of patients at risk and implicates PI3K/AKT signaling as a therapeutic target.
Wilson GD, Johnson MD, Ahmed S, Cardenas PY, Grills IS, Thibodeau BJ. Targeted DNA sequencing of non-small cell lung cancer identifies mutations associated with brain metastases. Oncotarget. 2018 May 25;9(40):25957-25970. doi: 10.18632/oncotarget.25409. eCollection 2018 May 25. PubMed PMID: 29899834; PubMed Central PMCID: PMC5995256.