Targeted DNA sequencing of non-small cell lung cancer identifies mutations associated with brain metastases
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George D. Wilson1,2, Matthew D. Johnson1,4, Samreen Ahmed2, Paola Yumpo Cardenas3, Inga S. Grills1 and Bryan J. Thibodeau2
1Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA
2Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI, USA
3Cancer Genetics Program, William Beaumont Hospital, Royal Oak, MI, USA
4Department of Radiation Oncology, McLaren Health Care, Macomb, MI, USA
George D. Wilson, email: [email protected]
Keywords: non-small cell lung cancer; brain metastases; next generation DNA sequencing; targeted agents; radiotherapy
Received: January 15, 2018 Accepted: April 24, 2018 Published: May 25, 2018
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.
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