Author of

• 30723

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  P1.03 - Biology (ID 161)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30736

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    P1.03-13 - Genomic Landscape of Brazilian Non-Small Cell Lung Cancer (ID 1296)

    09:45 - 18:00  |  Author(s): Adriane Feijó Evangelista
    • Abstract

    Background
    

    Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer with low survival rates. Therefore, NSCLC patients may be benefited by tailored treatment based on genomic profiling. However, the genomic landscape of Brazilian NSCLC remains unknown. Thus, our aim was to evaluate the genomic profiling of NSCLC of a Brazilian series.

    Method
    

    We analyzed 96 NSCLC patients from Barretos Cancer Hospital, Brazil. Exome sequencing of paired tumor/blood DNA was performed by Illumina HiSeq2500^™ and VarScan was applied for germline alterations exclusion, variant calling, and annotation. Cancer Genome Interpreter was employed for identification of driver genes. Mutational Signatures were performed using Somatic Signature. Copy Number Variations (CNV) were determined using Circular Binary Segmentation. Gene expression analysis was assessed by NanoString and pathway enrichment was performed using KEGG.

    Result
    

    Overall, 61 cases were adenocarcinomas, 34 squamous cell carcinomas and 1 was adenosquamous (I, n=19; II, n=14; III, n=23; IV, n=40). Regarding smoking, 82 patients were current/former smokers and 12 patients were never smokers and most of the cases presented the mutational signature 4. More than 30,000 mutations were identified and 733 were classified as drivers (known: 90; predicted: 643). TP53 gene was the most recurrently mutated gene (56% of the cases). Besides of TP53 gene, recurrent mutations were found in KRAS (23%), EGFR (12.5%), NFE2L2 (9%), HERC2 (9%), STK11, ROS1, PIK3CA and CDKN2A (8%). KRAS, EGFR, STK11 and ROS1 mutations were mutually exclusive. CNV gain was observed in 1q21.3, 1q22, 3q26, 31q29, 7q11.21, 7p11.1-q11.1, 8p11.1-q11.1, 19q13. Downregulation of DKK1, IBSP, LAMC2, NGFR and LAMB3 and upregulation of LAMC3, MAPK8IP1, IL5RA, NR4A1, AXIN2, PLA2G4E, COL6A6, CACNA2D2, LRP2, NR4A3, FOS, BMP5, and FGFR2 were observed in disease stages I/II indicating enrichment of PI3K-Akt, MAPK, Ras, Rap1 and Wnt signaling pathways. Downregulation of MCM2, VEGFA, E2F1, HMGA1, CCNE1, CHEK1, RAD51, FOSL1, CCNB1, GNG4, IL11 and IL8 and upregulation of WNT10B, MAPK10, GNG7, WNT4, IL7R, PIK3CG, and FGFR2 were observed in never smokers indicating enrichment of Cell cycle, Pathways in cancer and PI3K-Akt signaling. Differential expression of KRAS-mutated tumors indicated enrichment of ECM-receptor interaction, Focal adhesion, and PI3K-Akt pathway and TP53-mutated tumors indicated enrichment of Cell Cycle.

    Conclusion
    

    The genomic profiling of Brazilian NSCLC indicated remarkable driver mutations and genomic amplifications. Gene expression profiling indicates the enrichment of key pathways enrolled in TP53- and KRAS-driven tumors. Our results may contribute for improving the knowledge about the molecular pathogenesis of Brazilian NSCLC.

• 30780

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  P2.03 - Biology (ID 162)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30787

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    P2.03-07 - Frequency of Driver Genes (EGFR, KRAS, BRAF, ALK, RET and ROS1) Alterations in Brazilian Patients with Lung Adenocarcinoma (ID 1841)

    10:15 - 18:15  |  Author(s): Adriane Feijó Evangelista
    • Abstract

    Background
    

    Lung cancer is the deadliest cancer in the world. Several oncogenic drivers are observed in non-small cell lung cancer (NSCLC) and they have been used as therapeutic targets. The frequency of the major driver genes in lung adenocarcinoma varies based on ethnicity and the impact in the Brazilian admixture population has not been explored. Thus, we aimed to investigate the presence gene mutations of EGFR, KRAS, and BRAF, and ALK, RET and ROS1 rearrangements in Brazilian lung adenocarcinoma and to associate the presence of these alterations with clinicopathological characteristics and genetic ancestry.

    Method
    

    We evaluated 444 patients diagnosed with lung adenocarcinoma at Barretos Cancer Hospital. The presence of EGFR, KRAS and BRAF mutations in hotspot regions were evaluated by direct sequencing. For EGFR/KRAS/BRAF wild-type samples, we investigated the presence of ALK, RET and ROS1 rearrangements by the NanoString platform. Genetic ancestry was assessed by a multiplexed 46-ancestry informative markers panel. Stats: X² test and Cox regression model.

    Result
    

    Overall, 232 were male (52%) and 212 female (48%) and the average mean at diagnosis was 61 years. The majority of the patients were self-reported as white (77%), smokers (68%) and most patients were diagnosed at stage IV (74%). The median overall survival in patients at stage IV was 8.8 months. The frequency of EGFR mutations was 22.7% (n=101) and they were independently associated with never-smokers and Asian ancestry. KRAS mutations were found in 20.4% (n=91) of cases and were independently associated with smoking. The frequency BRAF mutations was of 1% (n=4), being all of them non-V600 BRAF. The frequency of ALK rearrangements was 2.25% (n=10) and was associated with younger age, the presence of metastases and advanced disease stage at diagnosis. RET and ROS1 rearrangements were only observed in 0.2% each (n=1/each) of cases. All the alterations identified in the oncogenic drivers were mutually exclusive.

    Conclusion
    

    The evaluation of the major driver genes for NSCLC, EGFR, KRAS, BRAF, ALK, RET and ROS1 can guide better clinical strategies for Brazilian lung adenocarcinoma, and the frequencies observed of these genes are in line with reported in other populations.