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Zhi Xie



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    MA24 - Genomic Evolution, KEAP 3 and More Non-Coding RNA (ID 928)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 BD
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      MA24.01 - Genomic Evolution Trajectory Depicts Invasiveness Acquisition from Pre-invasive to Invasive Adenocarcinoma (ID 11840)

      10:30 - 10:35  |  Author(s): Zhi Xie

      • Abstract
      • Presentation
      • Slides

      Background

      Accumulation of molecular abnormalities may depict evolution trajectories of tumor initiation and development. However, the genomic profile of early stage adenocarcinoma and molecular mechanism of invasiveness acquisition from pre-invasive to invasive adenocarcinoma remains barely explored.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We simultaneously collected 20 patients with adenocarcinoma in situ (AIS) (n=5), minimally invasive adenocarcinoma (MIA) (n=5) and stage IA adenocarcinoma (lepidic/acinar predominant) (n=10). Whole exon sequencing (WES) was performed in pre-invasive adenocarcinoma with multi-region specimens and stage IA adenocarcinoma. Analysis of genomic alteration among different pathological status was performed and tumor mutation burden (TMB) was calculated as well as six mutation types individually. Enriched pathways of each pathology were measured through KEGG analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      Baseline characteristics was generated through heatmap with smokers (2/20, 10%) and EGFR mutation (13/20, 65%) among whole population. AIS/MIA indicated much lower number of mutations than invasive adenocarcinoma (IAC) while TMB revealed the same trend without statistical significance. Multi-region sequencing showed high heterogeneity of single nucleotide variation (SNV) in AIS and MIA. Unique SNV presented dominant proportion in initial status. Cluster analysis showed higher copy number variation in AIS/MIA than IAC with cell adhesion molecules (CAMs) enriched in AIS/MIA while variety pathway enrichment in IAC through KEGG analysis. C>A transversions held major proportion in early stage adenocarcinoma and a significant increase in the proportion of C>T and C>G mutation was exhibited when evolving into IAC.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      Intratumor heterogeneity may occur in the very beginning of adenocarcinoma. High copy number variation was dominant event for AIS/MIA while higher tumor mutation burden was seen in IAC. Tobacco signature encompassing C>A transversions dominates the early development of adenocarcinoma and APOBEC signature may play a potential role in acquisition of cancer invasiveness.

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