Alterations of LKB1 and KRAS and Risk of Brain Metastasis: Comprehensive Characterization by Mutation Analysis, Copy Number, and Gene Expression in Non-Small-Cell Lung Carcinoma.
BACKGROUND: Brain metastases are one of the most malignant complications of lung cancer and constitute a significant cause of cancer related morbidity and mortality worldwide. Recent years of investigation suggested a role of LKB1 in NSCLC development and progression, in synergy with KRAS alteration. In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC.
MATERIALS AND METHODS: Patients treated at University of North Carolina Hospital from 1990 to 2009 with NSCLC provided frozen, surgically extracted tumors for analysis. GE was measured using Agilent 44,000 custom-designed arrays, CN was assessed by Affymetrix GeneChip Human Mapping 250K Sty Array or the Genome-Wide Human SNP Array 6.0 and gene mutation was detected using ABI sequencing. Integrated analysis was conducted to assess the relationship between these genetic markers and brain metastasis. A model was proposed for brain metastasis prediction using these genetic measurements.
RESULTS: 17 of the 174 patients developed brain metastasis. LKB1 wild type tumors had significantly higher LKB1 CN (p
CONCLUSION: LKB1 CN in combination with KRAS mutation predicted brain metastasis in NSCLC.
Published In/Presented At
Zhao, N., Wilkerson, M. D., Shah, U., Yin, X., Wang, A., Hayward, M. C., & ... Hayes, D. N. (2014). Alterations of LKB1 and KRAS and risk of brain metastasis: Comprehensive characterization by mutation analysis, copy number, and gene expression in non-small-cell lung carcinoma. Lung Cancer (Amsterdam, Netherlands), 86(2), 255-261. doi:10.1016/j.lungcan.2014.08.013
Hematology | Medical Sciences | Medicine and Health Sciences | Oncology
Department of Medicine, Hematology-Medical Oncology Division, Department of Medicine Faculty