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Jinjin Wang



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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-100 - Different Genetic Mutations Enriched in Circulating Tumor DNA Predict Different Metastatic Sites in Lung Adenocarcinoma Patients (ID 13636)

      16:45 - 18:00  |  Author(s): Jinjin Wang

      • Abstract

      Background

      The mutation map of the lung adenocarcinoma is clear. However, differences of genetic mutations related to metastatic sites have not been addressed before and remain to be explored. Identification of mutation signature may help to predict metastasis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We reviewed 353 ctDNA samples from lung adenocarcinoma patients with definite metastasis at our institute. Somatic mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of 59 genes.

      4c3880bb027f159e801041b1021e88e8 Result

      All the samples were divided into 2 groups based on the distance of the metastases: 165 samples was in the distal metastasis group including bone or liver metastases; 188 samples was in the proximal group, including lung, pleural or thoracic lymph node metastasis. The gene mutation number of the distal metastasis is higher than the proximal metastasis (4.92 vs 3.85, P=0.031). Gene mutations for each group are shown in the figure below. Similar to the genetic profiling of lung adenocarcinoma in COMIC database, the most frequently mutated genes were EGFR and TP53 in two groups. But the frequency mutation of NTRK1 in proximal metastasis group is three times more than that of the distal metastasis group (11/188, 5.9% vs 3/165,1.8%). And the frequency of ALK mutation in the distal metastasis group is two times more than that of the proximal metastasis group (10/165, 6.1% vs 6/188, 3.2%). Moreover, for the top 9 frequently mutant genes, there was 78% overlap in the two groups. However, the overlap with COSMIC database was 55% for distal metastasis group and 44% for the proximal metastasis.

      Distant metastasis group

      Proximal metastasis group

      COSMIC database

      gene

      Mutation frequency

      gene

      Mutation frequency

      gene

      Mutation frequency

      1

      EGFR

      70.30%

      EGFR

      73.94%

      EGFR

      31%

      2

      TP53

      60.61%

      TP53

      61.17%

      TP53

      31%

      3

      KRAS

      11.52%

      ERBB2

      9.04%

      KRAS

      18%

      4

      RB1

      10.30%

      KRAS

      9.04%

      STK11

      8%

      5

      NF1

      9.70%

      RB1

      7.45%

      CDKN2A

      7%

      6

      ERBB2

      7.88%

      NF1

      7.40%

      SMARCA4

      6%

      7

      APC

      6.67%

      APC

      6.91%

      NF1

      6%

      8

      ALK

      6.06%

      PIK3CA

      6.38%

      ATM

      5%

      9

      ATM

      6.06%

      RET

      5.85%

      KDR

      5%

      10

      PIK3CA

      6.06%

      NTRK1

      5.85%

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung adenocarcinoma patients with ALK mutation are more likely to have distant metastasis. While the patients with NTRK1 mutation are more likely to have proximal metastasis.

      6f8b794f3246b0c1e1780bb4d4d5dc53