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Honglin Guo



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    P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.12-14 - Genomic Profiling of Chinese Small Cell Lung Cancer and the Implications for Therapy (ID 14425)

      12:00 - 13:30  |  Author(s): Honglin Guo

      • Abstract

      Background

      Small cell lung cancer (SCLC) is one of the deadliest malignancies and accounts for nearly 15% of lung cancers. The 5-year survival rate for SCLC is very low. Previous study had revealed the genomic characterization of SCLC in Western patients. However, little is known about that in Chinese SCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      FFPE tumor and matched blood samples of 79 Chinese SCLC patients, including 60 males (median age of 60 years old) and 19 females (median age of 59 years old), were collected for next generation sequencing to detect 450 cancer related genes. All histological diagnoses were confirmed by independent pathologists. Genomic alterations including single nucleotide substitutions (SNV), short and long insertions/deletions (Indel), copy number variations (CNV), and gene rearrangement in selected genes were assessed.

      4c3880bb027f159e801041b1021e88e8 Result

      The most frequently altered genes in 79 Chinese SCLC patients were TP53 (94.9%), RB1 (83.5%), LRP1B (22.8%), KMT2D (13.9%), NOTCH1 (12.7%), FAM135B (11.4%), FAT1 (11.4%), KDR (11.4%), SPTA1 (10.1%) and STK24 (10.1%). Four of the patients harbored EGFR alterations including one EGFR fusion. Copy number variation analysis revealed that the most frequent variations occurred in the long arm of chromosome 13, including amplifications of STK24, FGF14, IRS2 and TNFSF13B (10.1%, 8/79, located at 13q32~13q34) and deletion of RB1 and BRCA2 (59.5%, 47/79, located at 13q13~13q14). Compared to the previously reported 25% mutational frequency in Western cohort reported previously, 31.6% (25/79) of our patients exhibited alterations in NOTCH signaling pathway related genes (NOTCH1, NOTCH2, NOTCH3, NOTCH4, EP300 and CREBBP). Around 15.2% (12/79) patients had PI3K/AKT/mTOR signaling pathway alterations (PIK3CA, MTOR, PTEN, and TSC2). Homologous Recombination Deficiency (HRD) related genes altered in 17.7% (14/79) patients, suggesting the potential clinical benefits from PARP inhibitors. The genomic alterations of FGF family members occurred in 25.3% (20/79) of patients. Other targetable genes included KIT (7.6%, n = 6), PDGFRA (5.1%, n = 4) and DDR2 (2.5%, n = 2).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this study, we characterized the genomic alteration profile of Chinese SCLC patients. Our discovery of CNV in the long arm of chromosome 13 might be helpful in understanding the pathogenesis of SCLC. Consistent with previous report, high mutation rates of TP53 and RB1 are the most important genomic features of SCLC [PMID: 26168399]. In addition, we also found several targetable gene variations including HRD, FGF family, KIT, PDGFRA and DDR2, which might provide potential targeted therapy options for SCLC patients. Further association analyses of these genomic alterations with clinical features in SCLC are still needed.

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