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Qiaoyun Tan



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    P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)

    • 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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      P2.17-13 - Genome-Wide Copy Number Alterations Profiling Predict Efficacy of Resected Stage II-IIIA Lung Adenocarcinoma  (ID 13314)

      16:45 - 18:00  |  Author(s): Qiaoyun Tan

      • Abstract
      • Slides

      Background

      The efficacy of platinum-based adjuvant chemotherapy(PBAC) varies for stage II-IIIA resected lung adenocarcinoma(RLUAD) patients, which necessitates the discovery of new potentially prognostic biomarkers. As a major source of genomic variations driving tumor evolution, somatic copy number alterations(CNAs) screening may identify predictive biomarkers.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The patterns of CNAs were analyzed by Oncoscan MIP array on formalin fixed paraffin embedded(FFPE) tumor specimens collected from 163 consecutive stage II-IIIA RLUAD patients, 145 out of which received PBAC.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 163 patients, 91(55.8%) relapsed within three years after surgery. The most frequent aberrations identified were 1q, 5p, 5q, 7p, 8q, 14p, 16p, 17q, 20q for copy number gains and 8p, 9p, 13p, 16q , 18q for losses. GISTIC2 analysis generated 45 amplification peaks and 40 deletion peaks, including some significantly mutated genes TERT, EGFR, MYC, CCND1, CDK4, MDM2, ERBB2, NKX2-1, CCNE1, CDKN2A, most of which were consistent with TCGA database. It was found that amplifications of 12p12.1(CMAS, GOLT1B, GYS2, LDHB, RECQL, ETNK1, IAPP, PYROXD1, KRAS)and KDM5A were associated with worse prognosis in our cohort(table), and validated in 506 LUADs from TCGA. 163 patients could be well classified into 4 groups with significantly different clinical outcomes based on thresholded copy number at reoccurring alteration peaks from GISTIC2 analysis. Among the 145 received PBAC patients, focal amplification of ERBB2 and deletion of 4q34.3 were found to be specific in relapsed patients compared with unrelapsed patients,This result was validated in an independent 183 cases corhort in Imielinski et al, indicating these two CNAs may contribute to RLUAD recurrence.

      Amplifications of 12p12.1 and KDM5A associated with overall survival

      Characteristics

      Univariate analysis

      (Amp vs Non-Amp)

      Multivariate analysis

      (Amp vs Non-Amp)

      Genes

      Location

      HR (95% CI)

      p

      HR (95% CI)

      p

      CMAS

      12p12.1

      1.99 (1.22~3.23)

      0.006

      2.80 (1.60~4.88)

      <0.001

      GOLT1B,GYS2,LDHB,RECQL

      12p12.1

      1.87 (1.14~3.07)

      0.014

      2.48 (1.41~4.37)

      0.002

      ETNK1

      12p12.1

      1.79 (1.10~2.93)

      0.020

      2.26 (1.60~3.94)

      0.004

      IAPP,PYROXD1

      12p12.1

      1.78 (1.07~2.94)

      0.025

      2.30 (1.30~4.07)

      0.004

      KRAS

      12p12.1

      1.74 (1.06~2.84)

      0.027

      2.14 (1.24~3.71)

      0.006

      KDM5A

      12p13.33

      1.67 (1.02~2.74)

      0.043

      1.88 (1.08~3.26)

      0.026

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study suggests that CNAs may be a potential prognostic classifier in RLAUD patients, amplifications of 12p12.1 and KDM5A might be prognostic biomarkers for RLUAD , and amplification of ERBB2 and deletion of 4q34.3 predicted early relapse after PBAC. These novel findings may provide implication for better clinical decision making.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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