Author of

• 31322

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  P2.11 - Screening and Early Detection (ID 178)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Screening and Early Detection
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 31338

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    P2.11-14 - Evolutionary Action Score of TP53 Predicts the Prognosis of Patients with Stage I Lung Adenocarcinoma (ID 53)

    10:15 - 18:15  |  Author(s): Zhendong Gao
    • Abstract

    Background
    

    Several studies have reported that TP53 mutations were associated with poor prognoses for patients with non-small-cell lung cancer. TP53 was reported to have a mutation rate of 46% in lung adenocarcinoma patients. Whether these mutations are of the same prognostic value is questionable. Here we use an algorithm named Evolutionary Action of TP53 (EAp53) which stratifies TP53 missense mutations into high-risk and low-risk groups based on the scores calculated to see whether different types of TP53 mutations are of prognostic value for patients with stage I lung adenocarcinoma.

    Method
    

    Whole-exome sequencing was performed on 83 patients who underwent surgery and with a pathologically confirmed adenocarcinoma between January 2011 and August 2013 at Fudan University Shanghai Cancer Center. No patient underwent neoadjuvant therapy. Missense TP53 mutations were classified to low-risk and high-risk groups according to their EAp53 score, which assesses the genotype-phenotype perturbation of point mutations. Patients were divided into 4 groups based on TP53 mutational status: wild-type TP53, truncating mutations, including frame-shift mutations, nonsense mutations, small indels, and splice-site mutations; high-risk missense mutations, defined as missense mutations with an EAp53 score >75.00; low-risk missense mutations, defined as missense mutations with an EAp53 score ≤75.00.

    Result
    

    Mutations of major driver genes, tumor suppressor genes and genes of interest for lung adenocarcinoma, including EGFR (60%), TP53 (35%), RB1 (7%), RBM10 (5%), NF1 (4%), CDKN2A (2%), ERBB2 (2%), KRAS (2%), PIK3CA (2%), SMARCA4 (2%), APC (1%), BRAF (1%), KEAP1 (1%) and STK11 (1%) were identified in our cohort of 83 stage I lung adenocarcinoma patients (fig 1a).

    TP53 mutations were identified in 29 patients (35%), with 11 high-risk, 9 low-risk, and 11 truncating mutations. Compared with patients with wild-type TP53, patients with TP53 mutations had a significantly lower tumor mutational burden (p < 0.001, fig 1b). Furthermore, there was a significant difference between the wild-type/low-risk group and the truncating/high-risk group (p < 0.001, fig 1b).

    Compared with the low-risk group, the high-risk group had significantly worse recurrence-free survival (p = 0.046), while there was no significant difference between the low-risk group and the wild-type group (p = 0.695, figure 1c). Moreover, when we combined the groups into a high-risk/truncating group and a low-risk/wild-type group, the high-risk/truncating group had a significantly worse recurrence-free survival (p = 0.0081, figure 3c) and overall survival (p = 0.0029, figure 1c).
    
    
    
    

    Conclusion
    

    TP53 mutational type is of prognostic value for patients with stage I lung adenocarcinoma.