Genetic Mutation Screen in Early Non-Small-Cell Lung Cancer (NSCLC) Specimens

作者：Bar Jair^*; Damianovich Maya; Siloni Goni Hout; Dar Erel; Cohen Yoram; Perelman Marina; Ben Nun Alon; Simansky David; Yellin Alon; Urban Damien; Onn Amir

来源：Clinical Lung Cancer, 2014, 15(2): 159-165.

DOI：10.1016/j.cllc.2013.11.005

• Co-mutation
• FFPE
• Sequenom
• Transitions
• Transversion

Mutations in early non-small-cell lung cancer (NSCLC) could determine prognosis. We tested for mutations in 22 genes in 96 early NSCLC specimens. A trend for worse outcome was found with a greater number of mutations and for smokers. KRAS and PIK3CA were the most common co-mutations. Our findings demonstrate the feasibility of large-scale genetic tests in early NSCLC. They might also suggest the importance of smoking cessation.
Background: Testing for genetic abnormalities in epithelial growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and potentially additional genes is a critical tool in the care of advanced NSCLC. There is conflicting evidence for the role of such tests in early NSCLC. We report a single-institute Sequenom testing for a wide range of mutations and their clinical correlations in early-resected NSCLC specimens. Materials and Methods: Early NSCLC paraffin-embedded, formalin-fixed (FFPE) specimens were collected, DNA extracted, and using Sequenom-based matrix-assisted laser desorption/ionization-time of flight analysis, mutations in 22 oncogenes and tumor suppressor genes were evaluated. Clinical data was collected retrospectively. Results: The technique was found to be feasible. Thirty-six of 96 patients (37.5%) had any genetic abnormality identified, and 8 (8.3%) had 2 or more mutations. Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR were the most common genes to appear mutated (15.6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) was the gene to be found most commonly in tumors with co-mutations. Transversions were found mostly in KRAS gene mutations and to be nonprognostic. No difference in the spectrum of mutations was found between squamous-cell and nonesquamous-cell lung cancers. Ever-smokers showed a trend for worse prognosis, with a similar spectrum of mutations. Conclusion: Sequenom-based mutation screen is feasible using FFPE samples. More than a third of the patients were found to harbor some genetic abnormality, and 8% were found to have more than a single mutated gene. Wide-range gene screens using large sample depositories are required for further insight into the important genes at play in early NSCLC.

• 出版日期2014-3