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• W2891963911 abstract "11584 Background: The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the development of targeted therapy for distinct molecular subsets. Activation of the β-catenin pathway is essential for colorectal carcinoma tumorigenesis and has been implicated in hepatocellular, thyroid and ovarian cancer. The β-catenin pathway is involved in the cell adhesion complex and Wnt signaling. While mutations in this pathway have been reported in NSCLC and β-catenin overexpression correlates with worse survival, its role in lung tumorigenesis is poorly understood. Methods: We performed targeted next generation sequencing using the Ion Torrent Hotspot Cancer Panel v.2 on tumor tissue from 244 NSCLC patients in which we have defined key demographic and clinical parameters including stage and survival. This cohort contained 91 Stage I cases with mRNA expression data using an Illumina platform. Co-occurrence of genes in the β-catenin pathway and 27 other genes in the panel were assessed by Fisher’s exact test, with Benjamini-Hochberg adjustment for multiple comparisons. Results: Seventeen of 244 tumors had mutations in the β-catenin pathway (APC, CTNNB1, and NOTCH1): 10/170 non-squamous NSCLC (6%, 95% CI 3%-10%), and 7/70 squamous NSCLC (10%, 95% CI 5%-19%). The rate of EGFR and RB1 mutations was higher in tumors with b-catenin pathway mutation (5/17 and 2/17) than in those without (13/227 and 0/227, adjusted p = 0.06 for both). The presence of an APC mutation was also associated with higher mRNA expression of the pro-survival protein, BCL2 (n = 91; 5/41 vs. 0/50, unadjusted p = 0.022, adjusted p = 0.3). Furthermore, APC mutations were more frequently observed in tumors with higher levels of EMT markers (high VIM 8% vs. low VIM 0%, unadjusted p = 0.16) and EMT transcription factors (10% vs. low expression 2%, unadjusted p = 0.16). Finally, we observed a trend toward worse overall survival in non-squamous tumors with mutations in the β-catenin pathway (n = 170, log rank test p = 0.07). Conclusions: These studies suggest that tumors with b-catenin pathway alterations are defined by a more mesenchymal and potentially drug resistant subtype which portends a poor prognosis." @default.
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• W2891963911 date "2017-05-20" @default.
• W2891963911 modified "2023-10-11" @default.
• W2891963911 title "Alterations in the Β-catenin pathway in non-small cell lung cancer to define a distinct molecular subtype with prognostic and therapeutic implications." @default.
• W2891963911 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.11584" @default.
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