Abstract 2166: The prevalence and molecular characteristics of EGFRlarge fragment deletion in Asian cancer population by comprehensive genome profiling

Abstract

Abstract Background: Large fragment deletion(LFD) of EGFR was associated with carcinogenesis in many types of cancers, especially in glioblastoma. Overall, there are five major types of EGFR large fragment deletion across EGFR extracellular region and carboxyl terminal domain which were originally discovered in gliomas. The prevalence and molecular feature of EGFR-LFD have not been studied in Asian Cancer population. Method: We retrospectively reviewed records of 66,500 Asian cancer patients who underwent genetic testing using capture-based targeted NGS between January 2014 to May 2020 at hospitals across China. Five to ten mL peripheral blood was collected from each patient in EDTA-coated tubes. Plasma was extracted within 2 hours of blood collection and shipped to the central testing laboratory. Formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks/sections or fresh tumor tissues were obtained from the hospitals, with confirmation by the pathologists for diagnosis and tumor purity. Mean sequencing depths of tumor tissue and plasma were 500X and 3000X respectively. Result: Our finding showed that EGFR-LFD was detected at a frequency of 0.03%, of which the most frequent was EGFRvIII in glioblastoma. In this EGFR-LFD cohort, there were 9 males(53%), 7 females(41%) and one unknown sex type with a median age of 54 years old, ranging from 42 to 85 years old. Interestingly, novel EGFR-LFDs spanning exon2-7 were identified in unreported cancer type including deletions of EGFR exon2-11(1case, lung cancer), exon2-15(1case, lung cancer), exon2-17(2 cases, lung cancer and colorectal cancer), exon2-28(1 case, cholangiocarcinoma). TERT promoter(TERTp) variants(60%) showed highest frequency in EGFR-LFD carriers, consisting of 6 cases of −124C>T and 2cases of −146C>T in glioblastoma(7) and melanoma(1). Concurrent EGFR amplification was identified in 67% of EGF-LFD cohort including glioblastoma(6), colorectal cancer(3), unknown(1). Over half of EGFR-LFD carriers harbored deletion on both arms of chromosome 10. Conclusion: Our study provided valuable insights into the distribution and molecular characteristics of EGFR-LFD by employing a large Asian Cancer cohort, hoping to shed lights on the treatment management for Asian EGFR-LFD carriers. Citation Format: Ruoying Yu, Qiuxiang Ou, Hua Bao, Xue Wu, Yang Shao. The prevalence and molecular characteristics of EGFRlarge fragment deletion in Asian cancer population by comprehensive genome profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2166.