Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Methylation profiling of EGFR mutant primary and metastatic lung cancer with brain metastasis.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20574)
Author(s): Yasin Mamatjan, Michael Cabanero, Jessica Weiss, Jeffrey Zuccato, Hadas Sorotsky, Ming Sound Tsao, Kenneth D. Aldape, Gelareh Zadeh, Frances A. Shepherd; MacFeeters Hamilton Center for Neuro-Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Princess Margaret Cancer Center, Toronto, ON, Canada; University Hospital Network (UHN) Biostatistics Department, Toronto, ON, Canada; MacFeeters-Hamilton Centre for Neuro-Oncology Research, Princess Margaret Cancer Center, Toronto, ON, Canada; Hadassah Hebrew University Medical Center, Jerusalem, Israel; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; The University of Texas MD Anderson Cancer Center, Houston, TX; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada
Background: EGFR-mutant lung cancer is a key molecular subtype of lung cancer. In recent years there is clear recognition in the value of using methylation signature of cancer for improving diagnosis and predicting outcome as well as understanding the biology of cancer progression. Methods: In this study we chose to characterize the methylome signature of early stage surgically resected EGFR-mutant lung adenocarcinomas in the primary lung tumor. 90 NSCLC cases and 7 matched metastatic brain samples were profiled using Illumina Infinium MethylationEPIC Beadchip. We compared methylation profiles of 1) smokers versus lifetime non-smokers and 2) matched primary lung versus brain metastasis to identify methylation biomarkers. We performed supervised analysis and unsupervised clustering of the methylation data. Results: Unsupervised clustering of all lung and brain samples based on 10K most variable probes showed a similar methylation signature between metastatic brain samples and lung samples. The 7-matched brain and lung samples formed close cluster groups based on matching pairs for the most variable probes from 2.5K to 10K, reflecting the same cell of origin. Supervised analysis of smokers versus lifetime non-smokers did not show any significant methylation differences between the two groups, while unsupervised analysis did not create clusters of smokers and non-smokers based on various number of probe sets we analyzed. Conclusions: Lung tumors that metastasized to the brain share similar methylation features with primary lung tumors. Comprehensive methylation profiling demonstrated no difference between EGFR mutant tumors in smokers versus non-smokers, suggesting that the EGFR mutation is a stronger determinant of outcome independent of smoking.