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Justyna Szumilo



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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-66 - Genomic Landscapes of DNA Copy Number Alterations in Primary Lung Cancers and Matched Brain Metastases (Now Available) (ID 1726)

      10:15 - 18:15  |  Author(s): Justyna Szumilo

      • Abstract
      • Slides

      Background

      Lung cancer (LC) is the leading cause of cancer mortality worldwide. The majority of LC patients will develop distant metastases at some point during their disease, and brain is among the most common sites of relapse. However, little is known about the mutational landscape of brain metastases (BM) and their potential inter-tumor heterogeneity. Better knowledge on this subject may pave the way to new therapeutic strategies. Here, we map the DNA copy number alterations (CNAs) by sequencing a cohort of primary LC samples and matched BM.

      Method

      The study group included 57 patients (21 females and 36 males, median age 61±8 years; 35 adenocarcinomas, 18 squamous-cell carcinomas, 2 large-cell carcinomas, 1 adenosquamous carcinoma and 1 small-cell lung cancer). From all patients pair-matched tissue samples from primary tumor and corresponding BM were collected, fixed in formalin and embedded in paraffin. All patients were therapy-naïve at the time of primary tumor collection. Genomic DNA was extracted using the QIAamp DNA FFPE Tissue Kit (Qiagen, Germany), followed by NGS library preparation using the NEBNext Ultra II DNA kit (NEB, USA). Samples were sequenced shallowly (average depth 26 Mreads) on the NextSeq 500 system (Illumina, USA). The R package QDNAseq was used to call and visualize DNA copy number levels. The P value of <0.05 (Wilcoxon paired test) was considered statistically significant.

      Result

      The median time between primary LC diagnosis and BM occurrence was 13 months range, 0 to 91 months), and synchronous BM were diagnosed in 12% of patients. Overall survival in the entire group was 22.5 months. The number of CNA was significantly higher in BM than in primary tumor, regardless of clinical/demographic data or type of aneuploidy (gains/losses). Primary tumors harbored significantly more gains and almost no losses. In both tumor sites, the most frequent gains affected 1q, 5p, 7p, 8q and 20q, whereas gains of 17q and 19q, and losses of 4p, 4q, 5q, 8p, 9p, 16q, 17p, 18q, 22q were identified only in BM. The fraction of the genome affected by mutational events in BM correlated positively with time to BM development. Three the top altered genes (IL7R, MLT11, SETDB1) were identical in both primary lesions and BM.

      Conclusion

      Our results indicate that while primary LC lesions harbor frequent amplifications, the CNA landscape of BM is dominated by deletion events. Higher number of CNA harbored by late compared to synchronous BM suggests high levels of genomic instability.

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