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Yu Chen



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-56 - Concurrent Mutations in Chinese Lung Cancer Patients Carrying HER2 Genomic Aberrations (ID 13756)

      16:45 - 18:00  |  Author(s): Yu Chen

      • Abstract
      • Slides

      Background

      Although human epidermal growth factor receptor 2 (HER2, ERBB2) genomic aberration has been identified as therapeutic targets, clinical trials of HER2-directed therapies have disappointing results in lung cancer. We hypothesize that the concurrent alterations might be one of the reasons, thus the aim of this study was to describe frequent concurrent alterations in Chinese lung cancer patients harboring HER2 mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 147 cancer patients with HER2 mutations were enrolled in the study. Tumor biopsy, ctDNA and pleural effusion samples were collected for detection alterations using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (59-1021).

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-two of 147 patients with HER2 genomic aberrations were diagnosed as lung cancer. The HER2 gene was amplified in 11 (18%) patients, whereas HER2 mutations were detected in 48 patients, co-occurrence of HER2 amplification and mutations were in 3 patients. Thirty of the 62 patients (48.39%) had concurrent actionable mutations across 18 genes, which involved in RTK-PIK3CA-mTOR signaling pathways, cell-cycle pathway, DNA repair pathway, RAS-RAF-MAPK pathway and some others (details in table). Moreover, 7 patients had more than 2 concurrent mutations besides HER2 mutation/amplification.

      Table 1. concurrent genetic alterations in HER2-altered lung cancer patients

      Signaling pathway

      Concurrent

      actionable

      mutations

      Number of

      patients

      RTK-PIK3CA-mTOR

      EGFR 11
      PIK3CA 4
      STK11 2
      FBXW7 1
      TSC1 1
      FLCN 1
      C11orf30 1
      Cell-cycle CDKN2A 5
      CCND1 2
      RB1 1
      DNA repair BRCA2 1
      ATM 1
      RAS-RAF-MAPK BRAF 1
      KRAS 1
      Others MDM2 2
      JAK2 2
      SMARCA4 2
      PTCH1 1

      8eea62084ca7e541d918e823422bd82e Conclusion

      Concurrent of actionable genetic alterations in HER2-altered Chinese lung cancer patients was common. The complex molecular profiles elucidate the importance of comprehensive analysis of genetic mutations when considering anti-HER2 targeted therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-09 - The Real World of NTRK Fusion Data in the Chinese Lung Cancer Populations: A Multicenter Study (ID 11307)

      16:45 - 18:00  |  Author(s): Yu Chen

      • Abstract
      • Slides

      Background

      NTRK fusions have been recently identified as a therapeutic target in a rare fraction of Caucasian patients with lung cancer (3.3%). The aim of this study was to evaluate the prevalence of NTRK fusions in Chinese lung cancer populations, which had not been reported earlier, and to describe targeting potential in Chinese lung cancer populations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A multicenter study in China was initiated from February 2014, and lung cancer patients have been enrolled as of December 2017. Capture-based comprehensive genomic profiling was performed on 2719 lung cancer FFPE samples (non-squamous/squamous/small=2061/349/309) sequenced to a mean coverage depth of > 650X for up to 381 cancer-related genes. Genomic alterations (GA) included short variant (SV) base subs and insertions/deletions, copy number alterations, and rearrangements/fusions. Tumor mutational burden (TMB; mut/Mb) was calculated on up to 1.2 Mb of sequenced DNA.

      4c3880bb027f159e801041b1021e88e8 Result

      Of this entire cohort, just one (0.04%) patient was identified with a TPM3-NTRK1 fusion. The patient was diagnosed with SCLC. TPM3-NTRK1 fusion was found by biopsy using NGS, the genes co-altered with NTRK fusion was no concurrent with KRAS, EGFR, ALK, ROS1, or other known drivers were identified in the study cohort cases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      NTRK fusions are a rare molecular subtype in Chinese lung cancer populations. Given clinical evidence for the activity of targeted therapy approaches, molecular eligibility for clinical trials of larotrectinib or entrectinib should include these fusion subtypes. The clinical evidence for responsiveness of NTRK fusions driven lung cancer provides an opportunity to personalize treatments and improve clinical outcomes for patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-39 - Next Generation Sequencing Reveals Genetic Landscape of Malignant Mesothelioma (ID 12702)

      16:45 - 18:00  |  Author(s): Yu Chen

      • Abstract
      • Slides

      Background

      Malignant mesothelioma (MM) is a rare form of cancer affecting the mesothelium lining. The 5-year survival rate of advanced patients is less than 1% due to the lack of effective medical therapies. To investigate the possibility of targeted therapy for MM patients, a deeper understanding of the genetic basis is required.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We reviewed 26 samples taken from 22 MM patients who underwent genetic testing at our institute from 2016 to the present. Somatic mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).

      4c3880bb027f159e801041b1021e88e8 Result

      The 26 samples included 8 tumor tissue samples, 17 blood samples and 1 ascetic fluid sample. The most frequently mutated genes were TP53 (11/21), followed by NF2 (6), RB1 (4), NF1 (3), FLT1 (3), BAP1 (2), EGFR (2), FAT2 (2), FGFR4 (2), KIT (2), MAP3K1 (2), MLL4 (2), STK11 (2), APC, ATR, BRAF, BRCA2, CDKN2A, ERBB3, FBXW7, MET, KRAS, PIK3CA and so on. Among these mutations, 5 of NF2 mutations and 2 of NF1 mutations were loss-of-function mutations, which suggests the possible sensitivity of mTOR inhibitors administration. Besides, patients with the active or inactive mutations of KRAS, BRAF, CDKN2A, ERBB3, MET and PIK3CA gene might be sensitive to corresponding targeted drugs. MET exon 14 skipping mutation, commonly identified in non-small-cell cancer (NSCLC) patients, had never been reported in MM patients before. c-Met inhibitors such as crizotinib and cabozantinib may be of efficacy for this patient. Apart from predicting therapeutic effectiveness of MEK inhibitors, the detection of KRAS activating mutation may also provide prognostic information.

      8eea62084ca7e541d918e823422bd82e Conclusion

      NGS can identify genetic mutations comprehensively and provide predictive and prognostic implications for MM patients. It is a cost-effective tool to describe the genetic landscape of MM, which will facilitate the development of novel therapeutics for the treatment of MM patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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