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W. Chen



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    MA17 - Genetic Drivers (ID 409)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      MA17.03 - Identifying Genomic Alteration and Inter-Tumor Heterogeneity of Multiple Primary Lung Cancers by Targeted NGS of Tumor Tissue and ctDNA (ID 4616)

      14:20 - 15:50  |  Author(s): W. Chen

      • Abstract
      • Presentation
      • Slides

      Background:
      Evidence supports the existence of genomic discrepancy in multiple primary lung cancers (MPLC). This study identified genomic alterations of MPLC by targeted next-generation sequencing (NGS) and assessed whether inter-tumor heterogeneous somatic mutations could be detected in circulating tumor DNA (ctDNA).

      Methods:
      94 tumor samples originating from 45 clinically considered multiple primary lung cancer patients (including multiple solid tumors and multifocal tumors) were available for genomic alteration analysis (NCT02833467). DNA and RNA were extracted from fresh tumor tissue or formalin-fixed, paraffin-embedded tissue. 143 cancer-related genomic alterations including single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs) and gene rearrangements were identified by Oncomine Comprehensive Panel (OCP), Ion Torrent techniques. High frequency clinical relevant mutations (EGFR, KRAS, BRAF, PIK3CA) were identified in circulating tumor DNA by droplet digital PCR (ddPCR).

      Results:
      The median age of the patients was 61 years and 71% were female. 91% patients were stageā… . Molecular analysis performed with a good quality. One hundred and thirty-six mutations and twenty four fusions were detected. Alterations were found in 81 of the 94 lesions (86%), involving EGFR (50.0%), TP53(10.6%), KRAS (8.5%), BRAF (4.3%), ERBB2 (4.3%), PIK3CA(2.1%),PTEN(2.1%),ALK (2.1%),ROS1 (1.1%), RET (7.4%), NF2(2.1%), CDKN2A(2.1%), APC(5.3%), ATM(5.3%),etc. Forty-two (93.3%) patients harbored discordant gene distribution between multiple tumors. CNVs were much higher in patients with more than 2 lesions. Forty-eight lesions harbored detectable somatic mutations by ddPCR, in which 30(62.5%) lesions were identified positive in circulating tumor DNA. 76.9% (20/26) solid dominant lesions were positive, which is significantly higher than ground glass opacity(GGO) dominant lesions(45.5%, 10/22, p=0.037). Figure 1



      Conclusion:
      Targeted NGS by OCP is feasible to detect multiple mutations simultaneously in early stage multiple primary lung cancers. Circulating tumor DNA has the ability to detect discordant somatic mutations and may represent of the overall mutational load and inter-tumor heterogeneity in multiple solid lung tumors.

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