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J. He



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    MA 15 - Lung Cancer Biology II (ID 670)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 15.07 - Consistency Analysis of Mutations in Tumor Tissue and Circulating Cell-Free DNA in Lung Cancer Patients Through next Generation Sequencing (ID 9759)

      15:45 - 17:30  |  Author(s): J. He

      • Abstract
      • Presentation
      • Slides

      Background:
      Remarkable advances for clinical diagnosis and treatment in cancers including lung cancer involve cell-free circulating tumor DNA (ctDNA) detection through next generation sequencing. However, before the sensitivity and specificity of ctDNA detection can be widely recognized, the consistency of mutations in tumor tissue and ctDNA should be evaluated. The urgency of this consistency is extremely obvious in lung cancer to which great attention has been paid to in liquid biopsy field.

      Method:
      Averagely 10 ml preoperative blood samples were collected from 30 patients containing pulmonary space occupying pathological changes by traditional clinic diagnosis. cfDNA from plasma, genomic DNA from white blood cells, and genomic DNA from solid tumor of above patients were extracted and constructed as libraries for each sample before subjected to sequencing by a panel contains 50 cancer-associated genes covering 1654 hotspots by custom probe hybridization capture with average depth >40000, 7000, or 6300 folds respectively.

      Result:
      Detection limit for mutant allele frequency in our study was 0.1%. The sequencing results were analyzed by bioinformatic expertise based on our previous studies on the baseline mutation profiling of circulating cell-free DNA and the clinicopathological data of these patients. Among all the 27 lung cancer patients, 80 percent were predicted as positive by ctDNA sequencing when the standard was defined as at least one of the hotspot mutations detected in the blood (ctDNA) was also detected in tumor tissue. Pneumonia and pulmonary tuberculosis were detected as negative according to the above standard. When evaluating all hotspots, 949 of 1265 (75 percent) mutations detected in tumor tissue were also detected in patients' blood. When evaluating all genetic variations, including those present at high levels in tumor tissue (clonal, driver genes in the panel) as well as those at low levels (subclonal, passenger genes in the panel), 327 of 583 (56 percent) detected in tumor tissue were also detected in patients' blood. Mutations detected only in blood (ctDNA and genomic DNA in white blood cells) but not in tumor tissue are not well understood yet.

      Conclusion:
      We demonstrated the importance of sequencing both circulating cell-free DNA and genomic DNA in tumor tissue for ctDNA detection in lung cancer. We also determined and confirmed the consistency of ctDNA and tumor tissue through NGS according to the criteria explored in our studies. Our strategy can initially distinguish the lung cancer from other space occupying lesions of lung. Our work shows that the consistency will be benefited from the optimization in sensitivity and specificity in ctDNA detection.

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