Possible correlation between SOCS1 methylation and EGFR exon 19 mutation but not exon 21 mutation in Chinese NSCLC patients

Abstract

18113 Background: Suppressor of cytokine signaling-1 (SOCS1) and -3 (SOCS3) interact with the epidermal growth factor receptor (EGFR) to bring about the ubiquination and degradation of the receptor. Silencing of SOCS1 and SOCS3 by methylation was postulated to regulate the IL-6R/JAK-mediated STAT3 activation. Its relationship to EGFR and EGFR mutations in lung cancer remains unclear. Here, we examined the relationship between EGFR mutations and methylation of SOCS1 and SOCS3 in Chinese NSCLC patients. Methods: EGFR mutations were assessed in DNAs from microdissected tumor cells. PCR products were purified and sequenced using the BigDye Terminator Cycle Sequencing Kit (Applied Biosystem) and the ABI 3100 Genetic Analyzer. For methylation analyses of SOCS1 and SOCS3, DNAs were extracted from paraffin sections of tumor tissues, bisulfite treated and analyzed by methylation- specific PCR (MSP). Results: Data is available from 9 lung cancer cell lines and 20 tumor samples. Five EGFR-wild type cell lines had methylation for SOCS1. We found EGFR exon 19 mutation in 5 (25%) tumors, exon 21 mutation (L858R) in 2 (10%) tumors, and 1 (5%) tumor had double mutations. Four of 5 (80%) tumors with exon 19 mutation and none (0%) of the tumors with exon 21 mutation had SOCS1 methylation, comparing to only 2 of 12 (17%) EGFR-wild type tumors had SOCS1 methylation. SOCS3 methylation was not detected in any of the primary tumors or cell lines. Conclusions: Our preliminary findings suggest that SOCS1 methylation might be positively correlated with EGFR exon 19 mutation but exclusive from exon 21 mutation. A following study with larger sample size is currently under way. SOCS1 methylation may explain the better tumor response associated with EGFR exon 19 mutation. No significant financial relationships to disclose.