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Jordan Karpus



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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.11 - Epigenomic Mapping of Cell-Free DNA in Patients with Non-Small Cell Lung Cancer (ID 14055)

      16:25 - 16:30  |  Author(s): Jordan Karpus

      • Abstract
      • Presentation
      • Slides

      Background

      Epigenetic modifications such as DNA methylation play an important role in human cancers, and have been implicated in tumor progression and drug resistance. Prior studies suggest 5-hydroxymethylcytosine (5hmC) has many important regulatory functions, given the colocalization of 5hmC within regulatory regions such as transcription factor binding sites, promotors and enhancers. Elevated 5hmC levels have been associated with increased gene expression. Genome-wide mapping of 5hmC has been performed in several different cells and tissues including brain and bone, though this has not previously been studied in lung cancer. It is possible the 5hmC profile can serve as a valuable biomarker for diagnosis, assessment for resistance, and surveillance for recurrence in non-small cell lung cancer (NSCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was an exploratory study with a primary objective to perform genome-wide 5-hydroxymethylcytosine profiling of circulating cell-free DNA (cfDNA) in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer. Thirty-three different patient samples were collected from 32 different patients with advanced NSCLC with a known EGFR mutation by prior tissue genotyping such as FoundationMedicine or cfDNA such as Guardant. Samples were classified as “controlled” if the disease burden was stable or decreasing, versus “uncontrolled” if disease burden was increasing. Patients ranged from previously untreated to heavily pretreated. Full profiling of 5hmC in cfDNA was performed.

      4c3880bb027f159e801041b1021e88e8 Result

      A difference in modification between “controlled” and “uncontrolled” disease was found in 311 differentially modified regions (p<0.01), and in 189 differentially modified genes(p<0.01).

      bestvina_iaslc_5_4_18.jpg

      Figure 1: Degree of methylation of a) 311 differentially modified regions b) 189 differentially modified genes.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In a retrospective analysis, a strong correlation exists between the methylation of specific regions and genes and the state of disease control. Future research should focus on if 5hmC profiling can be used to monitor disease status, to predict response to treatment, or alongside ctDNA for diagnostic accuracy.

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