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Maicon Fernando Zanon Da Silva



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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
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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): Maicon Fernando Zanon Da Silva

      • 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.