Author of

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  P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Small Cell Lung Cancer/NET
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36155

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    P47.15 - Mutational Landscape of Homologous Recombination Pathway in Small Cell Lung Cancer Patients (ID 1494)

    00:00 - 00:00  |  Presenting Author(s): Xin Li
    • Abstract
    • Slides

    Introduction
    

    The recent investigations of poly (ADP-ribose) polymerase inhibitors (PARPi) have improved the clinical response of a variety of solid tumors, including small cell lung cancer (SCLC). The presence of mutations in the DNA damage repair pathway, especially the pathway of homologous recombination (HR) was considered as the target of PARPi and a potential predictor for the improved benefit. Our study aimed to reveal the landscape of HR pathway mutations in a Chinese SCLC cohort and to explore the potential application of PARPi in SCLC patients.

    Methods
    

    Tissue samples were obtained from Chinese patients with small cell lung cancer who underwent targeted next-generation sequencing (NGS) in the laboratory of 3D Medicines, Inc. using a sequencing panel with more than 381 genes. Pathogenic or very likely pathogenic mutations of eleven HR pathway related genes including ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, FANCA, FANCD2, FANCG, RAD50, and RAD51 were analyzed. HR pathway mutation was defined as the occurrence of at least one mutation of the pathway related genes.

    Results
    

    The clinical information and genomic profiles of 117 SCLC patients were reviewed. There are 96 (82.1%) male and 21 (17.9%) female patients, with a median age of 63 (IQR range, 56-68). Mutations of TP53 and RB1 are the most commonly observed mutations in the studied SCLC cohort, with a frequency of 92.3% (108/117) and 72.6% (85/117), respectively. The overall prevalence of HR pathway mutation was 28.2% (33/117), with seven of the patients harbored at least two mutations in the pathway genes. The top mutated pathway genes are BRCA2 (12/117, 10.3%), FANCD2 (6/117, 5.1%), BRCA1 (5/117, 4.3%), and FANCA (5/117, 4.3%) in the overall population. Information of PD-L1 expression level as determined by tumor proportion score was available in 98 of the SCLC patients. None of the patients showed a strong-positive expression of PD-L1 (＞10%), and no significant difference of the positive PD-L1 expression rate was observed in patients with mutated HR pathway (1/28, 3.6%) compared to those with wild-type HR pathways (14/70, 20%) (p>0.05).

    Conclusion
    

    Our results indicated the wide presence of HR pathway mutations in patients with SCLC, which may contribute to the improved outcome from PARPi and facilitate the future development of PARPi in the treatment of SCLC.

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