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Zhiqi Yu

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    P57 - Tumor Biology and Systems Biology - Basic and Translational Science - DNA Repair (ID 195)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P57.04 - Mutations of DNA Damage Repair Genes in Lung Adenocarcinoma and Their Association with Actionable Alterations (ID 2123)

      00:00 - 00:00  |  Presenting Author(s): Zhiqi Yu

      • Abstract
      • Slides


      DNA damage repair (DDR) genes play key roles in the maintenance of human genomic stability. Increasing evidence showed that DDR gene dysfunction or defects are associated with the susceptibility and development of various types of cancers, including breast cancer and ovarian cancer. However, the mutation spectrum of genes involved in the DDR pathways and the clinical significance of these mutations in lung adenocarcinoma (LUAD) are still unclear.


      Whole exome sequencing data of 514 LUAD patients and RNA-seq data of paired LUAD tumor and normal tissues from 58 patients were downloaded from the TCGA database. We performed analyses on a list of 276 genes covering all major DNA repair pathways. We combined the results of deleterious mutations from exome sequencing and deep deletions from GISTIC calls for the analysis of loss-of-function mutation. The OncoKB knowledge database was used to identify actionable alterations. The R package Limma was used for differential expression analysis of tumor samples and normal samples.


      A total of 514 patients was enrolled and 351 of them (68.3%) had at least one genomic alteration of the DDR genes. The frequently mutated DDR genes included TP53 (29.8%), HERC2 (7.8%), NEIL2 (5.5%), NUDT18(5.3%), SMARCA4 (5.1%), WRN (5.1%), ATM(4.7%), FAN1(3.5%), PRKDC (3.1%), and NEIL3 (3.1%) as shown in Figure 1B. The most common type of alteration was deep deletions ( 50.6 %), followed by missense mutation ( 33.9 %), and nonsense mutation ( 8.3 %, Figure 1A). In DDR-mutated LUAD, 86.3% (303/351) of the patients possessed at least one actionable alteration, while 74.2% (121/163) of DDR wild-type LUAD patients harbored actionable mutations. Compared with DDR wide-type LUAD, patients with DDR-mutated LUAD had a higher rate of actionable mutation in PIK3CA, PDGFRA, KRAS, FGFR1 (Figure 1C). A total of 6 differentially expressed DDR genes were identified in DDR-mutated LUAD, in which RDM1, CDC25C, NEIL3, TTK, EXO1 were down-regulated and PPP4R4 were up-regulated (Figure 1D).figure 1.png


      The landscape of DDR mutations and their association with actionable alteration demonstrated that LUAD patients with altered DDR genes may benefit from precision medication guided by genetic sequencing results.

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