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Wu Zhuang



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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 13
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.03-01 - Molecular Spectrum of Patients with JAK1 Mutations in East Asian Non-Small Cell Lung Cancer (ID 188)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring JAK1 mutations.

      Method

      A total of 933 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK1 mutations and other genes were detected by next generation sequencing.

      Result

      JAK1 gene mutation rate was 1.50% (14/933) in non-small cell lung cancer, including D660G (2 patients), Q499E (1 patient), L954P (1 patient), C16* (1 patient), R239W (1 patient), S295* (1 patient), I359T (1 patient), E791K (1 patient), Q207L (1 patient), R69H (1 patient), H434Y (1 patient), K218N (1 patient) and E662Q (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were JAK1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 14.5 months and 13.0 months respectively (P=0.70); patients with (n=13) or without (n=1) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.64); patients with (n=5) or without (n=8) co-occurring KRAS mutations had a median OS of 11.0 months and 15.0 months respectively (P=0.79); patients with (n=3) or without (n=11) co-occurring NF1 mutations had a median OS of 11.0 months and 20.0 months respectively (P=0.11).

      Conclusion

      Althoght EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with JAK1 mutation in NSCLC patients, predict which patients may harbor JAK1 mutations, could have implications in triaging toward JAK1 variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.

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      EP1.03-03 - Association Between Molecular Spectrum of EZH2 Variants and Prognosis in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 93)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness in non-small-cell lung cancer (NSCLC) by EZH2 remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EZH2 mutations.

      Method

      A total of 1122 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EZH2 mutations and other genes were detected by next generation sequencing.

      Result

      EZH2 gene mutation rate was 0.62% (7/1122) in non-small cell lung cancer, including K515R (1 patient), I55M (1 patient), D142H (1 patient), K222N (1 patient), Q66R (1 patient), P486S (1 patient), and S652C (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EZH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 16.0 months and 20.0 months respectively (P=0.88); patients with (n=6) or without (n=1) co-occurring TP53 mutations had a median OS of not up to now and 20.0 months respectively (P=0.79); patients with (n=2) or without (n=5) co-occurring BRAF mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.45); patients with (n=2) or without (n=5) co-occurring SMARCA4 mutations had a median OS of 20.0 months and not up to now respectively (P=0.88).

      Conclusion

      EZH2 mutation may predict a worse prognosis of NSCLC. Methyltransferase inhibitor may be beneficial for NSCLC patients with specific EZH2 mutations. EGFR, TP53, BRAF, SMARCA4 gene accompanied may have less correlation with EZH2 mutation in NSCLC patients. The findings of this study could facilitate both clinical trial design and therapeutic strategies.

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      EP1.03-06 - POLD1 Mutations Define a Unique Molecular Class of Non-Small Cell Lung Cancer in Chinese Patients (ID 198)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Somatic POLE mutations have been found in a subset of non-small cell lung cancer (NSCLC) while POLD1 mutations are reportedly rare in NSCLC. The aim of this study is to investigate mutations and prognosis of NSCLC harboring POLD1 mutations.

      Method

      A total of 833 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of POLD1 mutations and other genes were detected by next generation sequencing.

      Result

      POLD1 gene mutation rate was 1.20% (10/833) in non-small cell lung cancer, including L357Rfs*36 (1 patient), R225H (1 patient), D76H (1 patient), I659M (1 patient), T582R (1 patient), A930T (1 patient), A749S (1 patient), G178V (1 patient), V455L (1 patient) and D102N (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were POLD1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=6) co-occurring EGFR mutations had a median OS of not up to now and 11.0 months respectively (P=0.11); patients with (n=8) or without (n=2) co-occurring TP53 mutations had a median OS of 13.0 months and 12.6 months respectively (P=0.80); patients with (n=2) or without (n=8) co-occurring NRAS mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.61); patients with (n=3) or without (n=7) co-occurring PTPRD mutations had a median OS of not up to now and 13.0 months respectively (P=0.79).

      Conclusion

      POLD1 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.

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      EP1.03-07 - Prevalence and Clinicopathological Characteristics of EIF1AX Mutations in Chinese Patients with Non-Small Cell Lung Cancer (ID 127)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. The prevalence of these mutations in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EIF1AX mutations.

      Method

      A total of 923 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EIF1AX mutations and other genes were detected by next generation sequencing.

      Result

      EIF1AX gene mutation rate was 1.30% (12/923) in non-small cell lung cancer, including D125N (1 patient), G6D (1 patient), R14G (1 patient), G15D (1 patient), W70C (1 patient), K3N (1 patient), G9D (1 patient), R13P (1 patient), R14S (1 patient), R57G (1 patient), G135E (1 patient), and P2L (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EIF1AX gene with co-occurring mutations. Among them, 11 patients with co-occurring mutations had a median OS of 20.0 months, and OS of one patient without complex mutations was 19.8 months. No statistically significant difference was found between the two groups (P=0.84). Briefly, patients with (n=2) or without (n=10) co-occurring TP53 mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.87); patients with (n=2) or without (n=10) co-occurring STK11 mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.02); patients with (n=3) or without (n=9) co-occurring NRAS mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.17); patients with (n=3) or without (n=9) co-occurring KRAS mutations had a median OS of not up to now and 20.0 months respectively (P=0.88).

      Conclusion

      There is no significant difference of molecular features in EIF1AX gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Next generation sequencing provides a simplified strategy and reasonably high detection rate for EIF1AX mutation, which suggested application of the strategies into clinical molecular diagnostics.

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      EP1.03-09 - Epidemiological Study of TSC1 Mutations Among Non-Small Cell Lung Cancer Patients in China (ID 115)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      The tuberous sclerosis complex 1 (TSC1) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in neoplasm. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TSC1 mutations.

      Method

      A total of 1106 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TSC1 mutations and other genes were detected by next generation sequencing.

      Result

      TSC1 gene mutation rate was 1.90% (21/1106) in non-small cell lung cancer, including Q654E (2 patients), R429K (2 patients), A1072D (1 patient), R850S (1 patient), E625K (1 patient), R715Q (1 patient), A84T (1 patient), S1038G (1 patient), M1090I (1 patient), D903H (1 patient), I143N (1 patient), Q3H (1 patient), L134F (1 patient), T1065M (1 patient), V407M (1 patient), S673F (1 patient), D675Y (1 patient), Q149H (1 patient) and T1144P plus L916M (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were TSC1 gene with co-occurring mutations. Briefly, patients with (n=12) or without (n=9) co-occurring TP53 mutations had a median OS of 14.0 months and 15.0 months respectively (P=0.58); patients with (n=9) or without (n=12) co-occurring KRAS mutations had a median OS of not up to now and 14.0 months respectively (P=0.56); patients with (n=2) or without (n=19) co-occurring BRAF mutations had a median OS of 18.5 months and 12.0 months respectively (P=0.71); patients with (n=4) or without (n=17) co-occurring CDKN2A mutations had a median OS of 8.0 months and 18.0 months respectively (P=0.47).

      Conclusion

      Accompanied gene has not well been connected with TSC1 gene mutations. Our finding expands the mutant spectrum of TSC1 gene and adds new understanding of the phenotype.

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      EP1.03-13 - Molecular Characteristics of East Asian Patients with VHL-Mutated Non-Small-Cell Lung Cancer: A Retrospective Study (ID 113)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration. However, the pathological or prognostic significance of VHL gene alteration has not been well defined in the other cancers, especially non-small cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring VHL mutations.

      Method

      A total of 972 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of VHL mutations and other genes were detected by next generation sequencing.

      Result

      VHL gene mutation rate was 0.72% (7/972) in non-small cell lung cancer, including W117fs*15 (1 patient), G44A (1 patient), G44V (1 patient), P81S (1 patient), R120T (1 patient), E51K (1 patient) and T100A (1 patient), and median overall survival (OS) for these patients was 22.0 months. Among them, all patients were VHL gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 22.0months and 12.0 months respectively (P=0.16); patients with (n=3) or without (n=4) co-occurring TP53 mutations had a median OS of not up to now and 12.0 months respectively (P=0.23); patients with (n=3) or without (n=4) co-occurring KRAS mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.07); patients with (n=2) or without (n=5) co-occurring SETD2 mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.01).

      Conclusion

      The present study expanded the database on VHL gene mutations in NSCLC and enriched the spectrum of known somatic mutations of the VHL gene. Chemotherapy may be considered as a possible treatment for carriers of the mutation. SETD2 mutated accompanied mutations might play a poor prognosis in VHL gene mutation NSCLC.

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      EP1.03-14 - Clinicopathologic Characteristics and Outcomes of Chinese Patients with Non-Small-Cell Lung Cancer and INPP4B Mutations (ID 109)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human non-small cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring INPP4B mutations.

      Method

      A total of 750 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of INPP4B mutations and other genes were detected by next generation sequencing.

      Result

      INPP4B gene mutation rate was 2.80% (21/750) in non-small cell lung cancer, including p.R623K (2 patients), p.N378S (1 patient), p.G187W (1 patient), p.V117I (1 patient), c.1721-1G>T (1 patient), p.R818* (1 patient), p.T829R (1 patient), p.Q753H (1 patient), p.L542M (1 patient), p.I68M (1 patient), p.Q814E (1 patient), p.K448N (1 patient), p.C617F (1 patient), p.Q600H (1 patient), p.G479* (1 patient), p.L155Q (1 patient), p.P572A (1 patient), p.L16V (1 patient), p.F652Y (1 patient), and p.T671S plus p.N228K (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were INPP4B gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=19) co-occurring EGFR mutations had a median OS of 20.0 months and 5.5 months respectively (P=0.01); patients with (n=17) or without (n=4) co-occurring TP53 mutations had a median OS of 15.0 months and 14.4 months respectively (P=0.68); patients with (n=7) or without (n=14) co-occurring PTPRD mutations had a median OS of not up to now and 15.0 months respectively (P=0.48); patients with (n=8) or without (n=13) co-occurring KRAS mutations had a median OS of 17.0 months and 15.0 months respectively (P=0.68).

      Conclusion

      INPP4B mutations were observed in 2.80 % of cases of NSCLC. INPP4B-mutated NSCLC can exhibit other driver gene alterations. No clinical characteristics were significantly associated with INPP4B mutation.

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      EP1.03-17 - Outcomes of Molecular Characteristics in Chinese BAP1-Mutant Non-Small Cell Lung Cancer Patients (ID 140)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. There is some clinical evidence for the use of BAP1 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring BAP1 mutations.

      Method

      A total of 851 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BAP1 mutations and other genes were detected by next generation sequencing.

      Result

      BAP1 gene mutation rate was 1.88% (16/851) in non-small cell lung cancer, including H94Y (1 patient), T177P (1 patient), E198Gfs*45 (1 patient), R238K (1 patient), D34Y (1 patient), Y173C (1 patient), E450K (1 patient), G41C (1 patient), S325F (1 patient), P293L (1 patient), Q28* (1 patient), E498K (1 patient), E631Q (1 patient), H144D (1 patient), Q280* (1 patient), (1 patient) and R518L (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were BAP1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=12) co-occurring EGFR mutations had a median OS of 14.5 months and not up to now respectively (P=0.35); patients with (n=9) or without (n=7) co-occurring TP53 mutations had a median OS of not up to now and 24.0 months respectively (P=0.79); patients with (n=3) or without (n=13) co-occurring CDKN2A mutations had a median OS of 24.0 months and not up to now respectively (P=0.57); patients with (n=4) or without (n=12) co-occurring KEAP1 mutations had a median OS of 5.0 months and 24.0 months respectively (P=0.07).

      Conclusion

      BAP1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of BAP1 aberrations is critical for the identification of therapeutic target candidates.

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      EP1.03-18 - Analysis of IDH1 Mutation Spectrum from Non-Small-Cell Lung Cancer in East Asian Patients (ID 95)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. IDH1 mutations are associated with the accumulation of the oncometabolite D-2-hydroxyglutarate, which acts as an epigenetic modifier, and the development of multiple malignancies. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring IDH1 mutations.

      Method

      A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH1 mutations and other genes were detected by next generation sequencing.

      Result

      IDH1 gene mutation rate was 1.23% (11/893) in non-small cell lung cancer, including Q138S (1 patient), D79V (1 patient), T373N (1 patient), C114* (1 patient), W336L (1 patient), I99M (1 patient), G104R (1 patient), R132C (1 patient), A193S (1 patient), Y34C (1 patient) and H67R (1 patient), and median overall survival (OS) for these patients was 11.0 months. Among them, all patients were IDH1 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now months and 8.5 months respectively (P=0.32); patients with (n=2) or without (n=9) co-occurring KMT2D mutations had a median OS of 11.5 months and 11.0 months respectively (P=0.80); patients with (n=5) or without (n=6) co-occurring KRAS mutations had a median OS of not up to now months and 8.0 months respectively (P=0.22); patients with (n=2) or without (n=9) co-occurring CREBBP mutations had a median OS of 15.5 months and 8.0 months respectively (P=0.67).

      Conclusion

      Our results demonstrated that decreased IDH1 gene mutation correlated with poor overall survival in NSCLC patients. IDH1 gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.

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      EP1.03-19 - The Frequency and Prognosis of MDM2 Mutations in East Asian Non-Small-Cell Lung Cancer Patients (ID 107)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      In neoplasm, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring MDM2 mutations.

      Method

      A total of 1152 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MDM2 mutations and other genes were detected by next generation sequencing.

      Result

      MDM2 gene mutation rate was 0.52% (6/1152) in non-small cell lung cancer, including D179N (1 patient), S84L (1 patient), T195M (1 patient), V234L (1 patient), A471S (1 patient) and E184Q (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were MDM2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 18.5 months and 24.0 months respectively (P=0.89); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 24.0 months and 7.0 months respectively (P=0.05); patients with (n=2) or without (n=4) co-occurring BRCA1 mutations had a median OS of 24.0 months and 13.0 months respectively (P=0.20); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 15.5 months and 24.0 months respectively (P=0.59).

      Conclusion

      MDM2 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that MDM2 mutations commonly co-existed with other driver genes. Our results show that MDM2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through MDM2 inhibition might offer new opportunities.

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      EP1.03-24 - Clinicopathologic Characteristics and Survival Outcome in Chinese Patients with Non-Small Cell Lung Cancer and HGF Mutations (ID 137)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor MET (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR). HGF and its receptor, MET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers, especially non-small cell lung caner (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring HGF mutations.

      Method

      A total of 526 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of HGF mutations and other genes were detected by next generation sequencing.

      Result

      HGF gene mutation rate was 4.56% (24/526) in non-small cell lung cancer, including E437K (1 patient) , L677I (1 patient), S386L (1 patient), R242Q (1 patient), H717N (1 patient), G520R (1 patient), R234H (1 patient), A713G (1 patient), P703S (1 patient), D264N (1 patient), N127K (1 patient), G506E (1 patient), C84* (1 patient), R647Q (1 patient), G133V (1 patient), D257N (1 patient), S386L (1 patient), S166R (1 patient), P27H (1 patient), C612* (1 patient), W528L (1 patient), G133V (1 patient), G694Wfs*31 (1 patient), and T143S plus G146A (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were HGF gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=20) co-occurring EGFR mutations had a median OS of not up to now and 20.0 months respectively (P=0.18); patients with (n=19) or without (n=5) co-occurring TP53 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.96); patients with (n=4) or without (n=21) co-occurring BRAF mutations had a median OS of not up to now and 20.0 months respectively (P=0.46); patients with (n=5) or without (n=19) co-occurring ERBB4 mutations had a median OS of 20.0 months and 19.6 months respectively (P=0.83).

      Conclusion

      EGFR, TP53, BRAF and ERBB4 gene accompanied may have less correlation with HGF 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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      EP1.03-28 - Frequency and Molecular Characteristics of BRCA1 Mutations in Non-Small Cell Lung Cancer from East Asian Patients (ID 145)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA1 mutations.

      Method

      A total of 730 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BRCA1 mutations and other genes were detected by next generation sequencing.

      Result

      BRCA1 gene mutation rate was 2.60% (19/730) in non-small cell lung cancer, including Y856H (3 patients), M1689T (2 patients), N909I (2 patients), G275D (2 patients), N473S (2 patients), S1217C (1 patient), M1628T (1 patient), E649* (1 patient), R1443* (1 patient), V191I (1 patient), I783V (1 patient), M669T (1 patient), and R71K (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were BRCA1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=16) co-occurring EGFR mutations had a median OS of 20.0 months and 13.0 months respectively (P=0.56); patients with (n=4) or without (n=15) co-occurring TP53 mutations had a median OS of 20.0 months and 19.5 months respectively (P=0.82); patients with (n=4) or without (n=15) co-occurring PIK3CA mutations had a median OS of not up to now and 13.5 months respectively (P=0.36); patients with (n=5) or without (n=14) co-occurring CDKN2A mutations had a median OS of not up to now months and 13.5 months respectively (P=0.28).

      Conclusion

      Our data reveal BRCA1 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA1 unclassified variants. Our results show that BRCA1 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through PARP inhibition might offer new opportunities.

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      EP1.03-35 - Prevalence, Clinicopathologic Characteristics, and Molecular Associations of IGF1R Mutations in East Asian Patients with NSCLC (ID 155)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring IGF1R mutations.

      Method

      A total of 812 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IGF1R mutations and other genes were detected by next generation sequencing.

      Result

      IGF1R gene mutation rate was 1.60% (13/812) in non-small cell lung cancer, including N977I (2 patients), S751T (1 patient), E1043D (1 patient), G171W (1 patient), E563K (1 patient), R275C (1 patient), F921[2>1] (1 patient), E712K (1 patient), R222W (1 patient), D1024A (1 patient), A760T (1 patient), and K533N (1 patient), and median overall survival (OS) for these patients was 9.0 months. Among them, all patients were IGF1R gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 6.0 months and 11.0 months respectively (P=0.10); patients with (n=12) or without (n=1) co-occurring TP53 mutations had a median OS of 18.0 months and 8.0 months respectively (P=0.68); patients with (n=4) or without (n=9) co-occurring KRAS mutations had a median OS of 14.5 months and 7.0 months respectively (P=0.76); patients with (n=5) or without (n=8) co-occurring NF1 mutations had a median OS of not up to now and 6.5 months respectively (P=0.24).

      Conclusion

      EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with IGF1R mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-46 - The KIF5B-RET Fusion as a Novel Mechanism of Acquired EGFR Tyrosine Kinase Inhibitor Resistance in Lung Adenocarcinoma (ID 103)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Lung cancer is a common malignancy and a leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. And most NSCLC patients with epidermal growth factor receptor (EGFR) mutations respond well to the treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Unfortunately, almost all patients with effective EGFR-TKIs therapy eventually develop drug resistance in about 1 year. The most common mechanism of acquired resistance to first-generation EGFR-TKI treatment is the development of the T790M mutation in exon 20 of the EGFR, which occurs in almost one half of cases of acquired resistance.

      Method

      In this case report, we present a 72-year-old male non-smoker patient with an EGFR exon 19 deletion diagnosed with lung adenocarcinoma (LADC), who initially responded to first-generation EGFR-TKI treatment, but developed acquired resistance, and was shown to have gene detected by the next generation sequencing.

      Result

      Repeated liquid biopsy showed the KIF5B-RET fusion gene by next generation sequencing. Therefore, cabozantinib was added to the treatment, and stable disease (SD) was achieved. Unfortunately, the patient did not acquire long-term benefits and the progression-free survival (PFS) was only 2 months

      Conclusion

      Our results suggested that the KIF5B-RET fusion gene is a possible novel cause of acquired resistance to first-generation EGFR-TKIs.

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      EP1.14-47 - Lung Adenocarcinoma with Concurrent KRAS Mutation and ALK Rearrangement Responding to Crizotinib (ID 108)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with EGFR or KRAS mutations.

      Method

      We reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by a NGS assay.

      Result

      Based on molecular findings, treatment was initiated with crizotinib in September, 2016. After 2 months of therapy, the patient achieved a partial response. Afterwards, the patient was further administrated with crizotinib for 9 months with a stable disease before tumor progression.

      Conclusion

      A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.

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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-34 - Survival Analysis of Icotinib for Brain Metastases in EGFR Mutated Non-Small Cell Lung Cancer (ID 112)

      08:00 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Survival and treatment options are limited for patients with brain metastases arising from non-small cell lung cancer (NSCLC). The aim of this study is to investigate the efficacy and survival analysis icotinib treatment for brain metastasis in non-small cell lung cancer patients with EGFR mutation.

      Method

      We retrospectively reviewed NSCLC patients with brain metastases who were treated with icotinib, and the survival rate was calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates. Univariate and multivariate factors for survival were analyzed by COX proportional hazards regression model.

      Result

      116 cases of rain metastases in EGFR mutated non-small cell lung cancer were female, less than 60 years old and non-smoking patients predominant; COX multivariate analysis found that histologic subtype and EGFR gene subtype were independent prognostic factors for these patients.

      Conclusion

      Icotinib showed promising efficacy in NSCLC patients with brain metastases. PFS and OS was longer in patients with adenocarcinoma than in those with a non-adenocarcinoma subtype. PFSand OS was longer in patients with EGFR common mutations than EGFR uncommon mutations.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-35 - Analysis of TET2 Gene Aberrations in East Asian Non-Small-Cell Lung Cancer Patients and Evaluation of Their Prognosis (ID 97)

      09:45 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      Ten-eleven translocation 2 (TET2) enzymes are frequently deregulated in cancer, but the genetic spectrum of TET2 mutation non-small cell lung cancer patients (NSCLC) patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TET2 mutations.

      Method

      A total of 895 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TET2 mutations and other genes were detected by next generation sequencing.

      Result

      TET2 gene mutation rate was 1.90% (17/895) in non-small cell lung cancer, including G126W (1 patient), E1477* (1 patient), I1871Nfs*4 (1 patient), T665K (1 patient), Y60F (1 patient), D932H (1 patient), M533I (1 patient), R1262W (1 patient), N71Kfs*5 (1 patient), Q769* (1 patient), W1198C (1 patient), Y1645Ifs*16 (1 patient), Q1532* (1 patient), R369W (1 patient), D648Y (1 patient), G1370V (1 patient) and T344K (1 patient), and median overall survival (OS) for these patients was 19.0 months. Among them, all patients were TET2 gene with co-occurring mutations. Briefly, patients with (n=15) or without (n=2) co-occurring TP53 mutations had a median OS of 19.0 months and 4.0 months respectively (P<0.01); patients with (n=3) or without (n=10) co-occurring CTNNB1 mutations had a median OS of 13.0 months and 19.0 months respectively (P=0.90); patients with (n=3) or without (n=10) co-occurring NF1 mutations had a median OS of not up to now months and 13.0 months respectively (P=0.87), patients with (n=3) or without (n=10) co-occurring KDM5C mutations had a median OS of not up to now months and 13.0 months respectively (P=0.75).

      Conclusion

      TET2 oncogenic activation through mutation defines a novel and distinct subset of NSCLC. CTNNB1, NF1 and KDM5C gene accompanied may have less correlation with KIT mutation in NSCLC patients. TP53 accompanied mutations might play a good prognosis in TET2 gene mutation non-small cell lung cancer.

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      P1.03-47 - KEAP1 Mutations in East Asian Patients with NSCLC: An Investigation of Prevalence, Clinicopathologic Characteristics and Prognosis (ID 104)

      09:45 - 18:00  |  Author(s): Wu Zhuang

      • Abstract

      Background

      The KEAP1/NRF2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring KEAP1 mutations.

      Method

      A total of 317 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of KEAP1 mutations and other genes were detected by next generation sequencing.

      Result

      KEAP1 gene mutation rate was 10.09% (32/317) in non-small cell lung cancer, including D618Tfs*54 (2 patients), W252L (1 patient), G158C (1 patient), D618Tfs*54 (1 patient), L237Q (1 patient), R415C (1 patient), K97N (1 patient), C368F (1 patient), A95T (1 patient), C273F (1 patient), S243F (1 patient), E149K (1 patient), H96L (1 patient), L70Q (1 patient), G558W (1 patient), E493K (1 patient), A40P (1 patient), E343V (1 patient), E219* (1 patient), G158C (1 patient), D235Tfs*3 (1 patient), I125T (1 patient), R320L (1 patient), R470H (1 patient), E244* (1 patient), G158V (1 patient), C368F (1 patient), I185F (1 patient), N157_M161del (1 patient), R336* (1 patient) and E219Q plus D526N (1 patient), and median overall survival (OS) for these patients was 13.5 months. Among them, all patients were KEAP1 gene with co-occurring mutations. Briefly, patients with (n=20) or without (n=12) co-occurring TP53 mutations had a median OS of 14.5 months and 13.5 months respectively (P=0.71); patients with (n=15) or without (n=17) co-occurring KRAS mutations had a median OS of 15.0 months and 12.0 months respectively (P=0.79); patients with (n=16) or without (n=16) co-occurring STK11 mutations had a median OS of 13.5 months and 18.0 months respectively (P=0.60); patients with (n=4) or without (n=28) co-occurring PIK3CA mutations had a median OS of not up to now and 12.0 months respectively (P=0.16).

      Conclusion

      KEAP1 gene mutation coexists with other gene mutation in NSCLC. TP53, KRAS, STK11 and PIK3CA gene accompanied may have less correlation with KEAP1 mutation in NSCLC patients. Analysis of KEAP1 mutations shows promise as a way to refine individual patients with NSCLC, and provides more insight into effective treatment strategies for patients with KEAP1 mutations.