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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5957 - EML4-ALK fusion variants associate with gender and age in Chinese NSCLC patients

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Wei Zhao

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

W. Zhao1, G. Liang2, L. Wang3, L. Dai2, D. Wu4, K. Wang4, A. Wang5, H. Chen6, Y. Dong7, M. Wang4

Author affiliations

  • 1 Department Of Thoracic Surgery, the First Affiliated Hospital of Kunming Medical University, 650031 - Kunming/CN
  • 2 Department Of Thoracic Surgery, First Affiliated Hospital of Guangxi Medical University, 530021 - Nanning/CN
  • 3 Department Of Thoracic Surgery, Fourth Hospital of Hebei Medical University, 050011 - Shijiazhuang/CN
  • 4 Department Of Thoracic Surgery, Sun yat-sen memorial hospital, Sun yat-sen University, 510120 - Guangzhou/CN
  • 5 Department Of Clinical Analysis, OrigiMed, 200000 - Shanghai/CN
  • 6 Department Of Bioinformatics, OrigiMed, 200000 - Shanghai/CN
  • 7 Origimed, OrigiMed, 200000 - Shanghai/CN
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Resources

Abstract 5957

Background

EML4-ALK fusion is one of the major activating kinase mutations in NSCLC. It occurs with varying frequency in different populations and is known to associate with clinical features such as smoking history and age. Based on different breakpoints in EML4 and ALK genes, there exist several fusion subtypes (variants), which have been reported to respond differently to ALK inhibitors. In this study, we investigated the landscape of EML4-ALK in Chinese NSCLC patients and correlated fusion variants with clinical factors.

Methods

FFPE tumor and matched blood samples of over 1000 Chinese NSCLC patients were collected for NGS-based 450 cancer genes panel assay. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements in selected genes were assessed.

Results

A total of 73 EML4-ALK fusion samples were identified. In our cohort, younger patients were more likely to harbor ALK fusions, consistent with previous reports. In terms of EML4-ALK fusion variants, we observed three major subtypes: 30 E6:E20 (variant 3) cases, 20 E13:E20 (variant 1), and 11 E20:E20 (variant 2). Interestingly, E6-E20 was enriched in male patients (18 vs 12), while E13-E20 was enriched in female patients (13 vs 7); furthermore, for the E13-E20 variant all 13 female patients were younger than 60, while 4 out of 7 male patients were older than 60 (p = 0.007). To complete the picture, other subtypes of EML4-ALK fusion in our cohort included: 4 E18:E20, 4 E14:E20, 3 E2:E20, and 1 E21:E20.

Conclusions

EML4-ALK fusion is known to associate with clinical features including race, age, and smoking history. Our profiling of EML4-ALK alteration in Chinese NSCLC patients not only revealed the composition of fusion subtypes, but also connected variants with demographic factors such as gender and age. Our initial results need to be validated in larger cohorts and/or different populations. Given that different fusion variants respond differently to ALK inhibitors, our findings could have important implications.

Clinical trial identification

Legal entity responsible for the study

OrigiMed.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

A. Wang, H. Chen, Y-A. Dong: Employee: OrigiMed. All other authors have declared no conflicts of interest.

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