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Jinhuo Lai



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.15 - Molecular Characteristics of ALK Primary Point Mutations Non-Small-Cell Lung Cancer in Chinese Patients (ID 14704)

      11:15 - 11:15  |  Author(s): Jinhuo Lai

      • Abstract
      • Slides

      Background
      Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung cancer at 3-7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease. While the genetic locus of ALK primary point mutations NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring ALK primary point mutations.

      A total of 339 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of ALK primary point mutation and other genes were detected by next generation sequencing.


      ALK gene primary point mutation rate was 8.55% (29/339) in non-small cell lung cancer, including V163L (3 patients), F921Gfs*16 (2 patients), K1416N (2 patients), A585T (2 patients), P1442Q (1 patient), A348T (1 patient), K1525E (1 patient), S737L (1 patient), P115L (1 patient), Q515E (1 patient), E314D (1 patient), R395H (1 patient), S1219F (1 patient), S341G (1 patient), P1543S (1 patient), G129V (1 patient), Q167H (1 patient), L550F (1 patient), T1012M (1 patient), D302Y (1 patient), H755Q (1 patient), H331Q (1 patient), G1474E (1 patient) and E119D (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, 27 patients with co-occurring mutations had a median OS of 20.0 months, and median OS of the 2 patients without complex mutations was 8.5 months. Statistically significant difference was found between the two groups (P=0.02). Briefly, patients with (n=8) or without (n=21) co-occurring EGFR mutations had a median OS of 24.0 months and 20.0 months respectively (P=0.73); patients with (n=21) or without (n=8) co-occurring TP53 mutations had a median OS of 20.0 months and 17.0 months respectively (P=0.83).

      EGFR and TP53 gene accompanied may have less correlation with ALK primary point mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.

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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 4
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.03-04 - Molecular Characteristics of ALK Primary Point Mutations Non-Small-Cell Lung Cancer in Chinese Patients (ID 11103)

      16:45 - 18:00  |  Author(s): Jinhuo Lai

      • Abstract
      • Slides

      Background

      Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung cancer at 3-7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease. While the genetic locus of ALK primary point mutations NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring ALK primary point mutations.

      Method

      A total of 339 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of ALK primary point mutation and other genes were detected by next generation sequencing.

      Result

      ALK gene primary point mutation rate was 8.55% (29/339) in non-small cell lung cancer, including V163L (3 patients), F921Gfs*16 (2 patients), K1416N (2 patients), A585T (2 patients), P1442Q (1 patient), A348T (1 patient), K1525E (1 patient), S737L (1 patient), P115L (1 patient), Q515E (1 patient), E314D (1 patient), R395H (1 patient), S1219F (1 patient), S341G (1 patient), P1543S (1 patient), G129V (1 patient), Q167H (1 patient), L550F (1 patient), T1012M (1 patient), D302Y (1 patient), H755Q (1 patient), H331Q (1 patient), G1474E (1 patient) and E119D (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, 27 patients with co-occurring mutations had a median OS of 20.0 months, and median OS of the 2 patients without complex mutations was 8.5 months. Statistically significant difference was found between the two groups (P=0.02). Briefly, patients with (n=8) or without (n=21) co-occurring EGFR mutations had a median OS of 24.0 months and 20.0 months respectively (P=0.73); patients with (n=21) or without (n=8) co-occurring TP53 mutations had a median OS of 20.0 months and 17.0 months respectively (P=0.83).

      Conclusion

      EGFR and TP53 gene accompanied may have less correlation with ALK primary point mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.

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      P1.03-26 - Analysis of DDR2 Gene Aberrations in Chinese Non-Small-Cell Lung Cancer Patients and Evaluation of Their Prognosis (ID 11105)

      16:45 - 18:00  |  Author(s): Jinhuo Lai

      • Abstract
      • Slides

      Background

      Recently, Mutations in discoidin domain receptor 2 (DDR2) gene were recently identified as promising molecular targets in non-small-cell lung cancer. While the genetic spectrum of DDR2 mutation NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring DDR2 mutations.

      Method

      A total of 283 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of DDR2 mutation and other genes were detected by next generation sequencing.

      Result

      DDR2 gene mutation rate was 3.18% (9/283) in non-small cell lung cancer, including S311N (3 patients), E44K (1 patient), R709Q (1 patient), T564I (1 patient), R742Q (1 patient), G206* (1 patient) and M117I (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were DDR2 gene with co-occurring mutation. Briefly, patients with (n=6) or without (n=3) co-occurring EGFR mutations had a median OS of 20.0 months and 9.0 months respectively (P=0.29); patients with (n=4) or without (n=5) co-occurring TP53 mutations had a median OS of 17.0 months and 21.5 months respectively (P=0.63); patients with (n=2) or without (n=7) co-occurring KRAS mutations had a median OS of 13.5 months and 20.0 months respectively (P=0.82); patients with (n=2) or without (n=7) co-occurring PTPRD mutations had a median OS of 15.0 months and 20.0 months respectively (P=0.96).

      Conclusion

      DDR2 mutations were observed in 3.18 % of cases of NSCLC. DDR2-mutated NSCLC can exhibit other driver gene alterations. No clinical characteristics were significantly associated with DDR2 mutation.

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      P1.03-27 - Somatic Mutations in BRCA2 Genes Are Associated with Prognosis in Chinese Non-Small-Cell Lung Cancer Patients (ID 11115)

      16:45 - 18:00  |  Author(s): Jinhuo Lai

      • Abstract
      • Slides

      Background

      The role of BRCA2 gene somatic mutations are mainly to maintain genome integrity in response to DNA damage through different mechanisms. Deregulation of BRCA2 is associated with the development of tumor and altered sensitivity to chemotherapeutic agents, but the genetic variability of BRCA2 somatic mutation NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA2 somatic mutations.

      Method

      A total of 362 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of BRCA2 somatic mutation and other genes were detected by next generation sequencing.

      Result

      BRCA2 gene somatic mutation rate was 4.97% (18/362) in non-small cell lung cancer, including S547P (2 patients), G1433W (2 patients), I488V (1 patient), C315S (1 patient), T2007S (1 patient), I1929V (1 patient), H3117Y (1 patient), G1370V (1 patient), T768S (1 patient), E2260Q (1 patient), R2087K (1 patient), E3167Q (1 patient), S163T (1 patient), T152I (1 patient), E2275Q (1 patient) and S163T (1 patient) , and median overall survival (OS) for these patients was 18.0 months. Among them, all patients were BRCA2 gene with co-occurring somatic mutation. Briefly, patients with (n=3) or without (n=15) co-occurring EGFR mutations had a median OS of 21.0 months and 18.0 months respectively (P=0.22); patients with (n=11) or without (n=7) co-occurring TP53 mutations had a median OS of 7.5 months and 18.0 months respectively (P=0.15); patients with (n=2) or without (n=16) co-occurring HER2 mutations had a median OS of 11.0 months and 20.0 months respectively (P=0.24).

      Conclusion

      BRCA2 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA2 unclassified variants. Our results show that BRCA2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through BRCA2 inhibition might offer new opportunities.

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      P1.03-28 - Association Between Molecular Characteristics of CTNNB1 Mutations and Prognosis in Patients with Nsclc in Chinese Patients (ID 11097)

      16:45 - 18:00  |  Author(s): Jinhuo Lai

      • Abstract
      • Slides

      Background

      Recently, CTNNB1, encoding beta-catenin, is a well-known tumor-related gene in the wnt signaling pathway. While the genetic variability of CTNNB1 mutation NSCLC patients is unclear.The aim of this study is to investigate mutations and prognosis of NSCLC harboring CTNNB1 mutations.

      Method

      A total of 677 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of CTNNB1 mutation and other genes were detected by next generation sequencing.

      Result

      CTNNB1 gene mutation rate was 1.92% (13/677) in non-small cell lung cancer, including S33F (4 patients), S33C (1 patient), D32H (1 patient), G34R (1 patient), G34V (1 patient), G34del (1 patient), D11G (1 patient), S45P (1 patient), S45F (1 patient) and S45del plus S33Y (1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were CTNNB1 gene with co-occurring mutations. Briefly, patients with (n=7) or without (n=6) co-occurring EGFR mutations had a median OS of 25.8 months and 8.5 months respectively (P=0.18); patients with (n=10) or without (n=3) co-occurring TP53 mutations had a median OS of 10.0 months and 17.5 months respectively (P=0.35); patients with (n=2) or without (n=11) co-occurring BRAF mutations had a median OS of 7.5 months and 13.0 months respectively (P=0.14); patients with (n=2) or without (n=11) co-occurring ATM mutations had a median OS of 17.5 months and 11.0 months respectively (P=0.53).

      Conclusion

      Accompanied gene has not well been connected with CTNNB1 gene mutations. Our finding expands the mutant spectrum of CTNNB1 gene and adds new understanding of the phenotype.

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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): Jinhuo Lai

      • 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.

      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.

      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.

      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.

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