Synonymous EGFR variant p.Q787Q is neither prognostic nor predictive in patients with lung adenocarcinoma

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• 作者：Jonas Leichsenring ; Anna-Lena Volckmar ; Nikolaus Magios ; Cristiano Manuel Morais de Oliveira ; Roland Penzel ; Regine Brandt ; Martina Kirchner ; Farastuk Bozorgmehr ; Michael Thomas ; Peter Schirmacher ; Arne Warth ; Volker Endris and Albrecht Stenzinger
• 刊名：Genes, Chromosomes and Cancer
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：56
• 期：3
• 页码：214-220
• 全文大小：198K
• ISSN：1098-2264

文摘

Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the Epidermal Growth Factor Receptor (EGFR) benefit from targeted therapies. A synonymous polymorphism (rs1050171, p.Q787Q) was shown to be associated with improved overall survival (OS) in colorectal cancer patients. As data in NSCLC are limited, we retrospectively analyzed associations of p.Q787Q with clinicopathological parameters including clinical response and outcome in patients with lung adenocarcinoma (ADC) who received tyrosine kinase inhibitor (TKI) therapy. Of 642 ADC patients whose tumors were profiled by next generation sequencing, 102 (15.9%) carried EGFR mutations targetable by TKIs (30.4% male patients, median age 65.1 y, 19.6% smokers with 12.8 median pack years). Seventy-nine patients (77.5%) received TKI therapy either as a first- or second-line therapy. Of the 102 EGFR-mutant tumors, 72 (70.6%) exhibited the p.Q787Q polymorphism and another 12 (11.8%) cases with p.Q787Q harbored an additional TKI insensitive mutation (p.T790M). The polymorphism was neither associated with classic clinicopathological parameters nor with overall survival (21.1 months vs. 20.1 months; P-value = 0.91) or clinical response (P-value = 0.122). The patients with p.T790M had worse survival compared to EGFR activating mutation carriers with and without p.Q787Q when analyzed as a separate group (27.5 months, P-value = 0.02). In conclusion, p.Q787Q is neither a suitable prognostic nor predictive biomarker for ADC patients receiving anti-EGFR therapy in first- or second-line of therapy.