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Yunjian Huang



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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 7
    • 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): Yunjian Huang

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

      08:00 - 18:00  |  Author(s): Yunjian Huang

      • 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): Yunjian Huang

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

      08:00 - 18:00  |  Author(s): Yunjian Huang

      • 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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      EP1.03-24 - 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): Yunjian Huang

      • 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): Yunjian Huang

      • 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): Yunjian Huang

      • 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.