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M. Gos



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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-004 - The Methylation Profiling of Multiple Tumor Suppressor Genes in Plasma Cell-Free DNA of Patients with NSCLC vs Benign Tumors (ID 5166)

      14:30 - 14:30  |  Author(s): M. Gos

      • Abstract
      • Slides

      Background:
      Effective discrimination between lung cancer and benign tumours is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. While most solitary pulmonary nodules are benign, around 20% of cases represent an early stage lung cancer. The presence of cell-free DNA (cfDNA) in plasma of lung cancer patients demonstrates promising diagnostic implications and could be considered as an auxiliary tool in the differential diagnosis of solitary pulmonary nodules by evaluating cancer-specific biomarkers, such as hypermethylated tumor DNA fragments. We developed a simultaneous methylation profiling of 21 distinct tumor suppressor genes (TSGs) in plasma cfDNA using MS-MLPA assay.

      Methods:
      The methylation profiling of 21 TSGs in plasma cfDNA of 32 resectable NSCLC (I-IIIa) patients and 8 subjects with benign lung nodules (hamartoma, fibrosis, granuloma) was performed using optimized MS-MLPA assay.

      Results:
      25/32 (78%) NSCLC and 8/8 (100%) benign-nodule cfDNA samples presented at least one TSG methylation, however the number of hypermethylated TSGs was much higher in NSCLC group. APC (frequency 18% samples), MLH1 (18%), ATM (13.6%), DAPK1 (13.6%), HIC 1 (13.6%), and RARβ (9%) were the most frequently methylated genes in NSCLC, while TIMP3 (75%), MLH1 (25%) and TP73 (37.5%) – in benign patients.

      Conclusion:
      The optimized MS-MLPA assay allowed simultaneous detection of multiple methylated TSGs in plasma cfDNA. The MS-MLPA showed good performance in samples with diverse cfDNA concentrations suggesting that methylation detection rate depends on the methylated DNA content in a sample. The study is on-going. The groups are to be extended and other benign lung pathologies evaluated.

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