Virtual Library

Start Your Search

Hongwei Duan

Author of

  • +

    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
    • +

      P1.02-051 - Ultra-Deep Sequencing Depicts the Genomic Landscape of Ground-Glass Nodules in Early Stage Lung Adenocarcinoma (ID 9252)

      09:30 - 16:00  |  Presenting Author(s): Hongwei Duan

      • Abstract

      Ground-glass nodule (GGN) is a type of nonspecific abnormality in lung parenchyma detected by computed tomography (CT) as hazy lesion with preservation of bronchial structures and vascular margins, which has a high correlation with lung adenocarcinoma. Different from typical lung cancer, malignant GGN appears a very early stage characteristic with long and indolent course. Large-scale radiological, pathological, and genetic studies on GGNs have broadened our knowledge to develop strategies of management. However, the molecular pathogenesis of GGNs remains unclear, leaving several questions of great clinical significance unsolved.

      Motivated by this, we collected a cohort of 29 GGN patients diagnosed as early stage lung adenocarcinoma and performed whole exome sequencing (WES) to clarify the comprehensive genomic features and underlying molecular mechanism of GGNs. With the expectation of low purity of these samples, we adopted an ultra-deep sequencing depth to ~1000x, which is the deepest WES strategy so far in a single sample of single sequencing experiment to our knowledge, and got a high resolution landscape of genomic alterations in GGNs.

      We found the extreme heterogeneity within each GGN patient, most of mutations manifesting as low frequency, indicating that GGNs grew under neutral evolutionary dynamics. Next we analyzed the mutation signature of these mutations and identified two novel signatures, Cp*C>A and Gp*CpC>T/Gp*CpG>T. These two signatures can reflect the mutation accumulating process within a growing tumor after initiation. Seven driver genes calculated in our cohort were all known lung cancer related genes, including EGFR,MGA,PIK3CA,PPP2R1A,RBM10,SETD and TP53. Of note, copy number alterations in GGNs were significantly less than other late stage lung cancers and this would result in the specific nature of GGNs.

      In summary, this analysis of exome sequencing data highlights the repertoire of cancer genes and mutational processes in GGN patients, and progresses towards a comprehensive account of the somatic genetic basis of GGNs. These results, combined with further study efforts, will accelerate the pace to the achievement of accurate diagnosis and treatment for GGN patients. Also, the endeavor here provides a framework for the research on early stage tumors and low purity tumors, which will become a subject of active investigation in the near future.