CCNE1 amplification is associated with liver metastasis in gastric carcinoma

Abstract

With targeted therapies becoming the new standard of care in oncology, next generation sequencing (NGS) is emerging as a valuable method for analyzing the molecular underpinnings of individual tumors. Cyclin E1, encoded by CCNE1 causes activation of E2F mediated transcription and drives cells from G1 into S phase with cyclin-dependent kinase 2 (CDK2). CCNE1 amplification has been found in 11–12% of gastric cancers, but the clinical significance of this amplification remains controversial, and its association with liver metastasis has not been studied.This study included 226 patients diagnosed with advanced gastric adenocarcinoma. We performed multi-gene panel tests containing 143 genes using DNA and RNA obtained from primary (n = 197; 120 endoscopic biopsies and 77 resections) or metastatic cancer tissues (n = 29; 26 biopsies, 2 excisions, and 1 fin. needle aspiration). Among the 226 cases, 28 cases (12.4%) had CCNE1 amplification, almost half of which (n = 13, 46.4%) showed liver metastasis. In patients with CCNE1 amplification (n = 28), TP53 mutations (n = 23, 82.1%) and ERBB2 amplification (n = 8, 28.6%) were the most frequent concurrent genetic alterations. In contrast, 42 (21.2%) of 198 patients without CCNE1 amplification showed liver metastasis. CCNE1 amplification was significantly associated with liver metastasis (p = 0.004; odds ratio, 3.219).Our results show that CCNE1 amplification is significantly associated with liver metastasis in a TP53-mutated gastric cancer subtype. Given the frequent association of CCNE1 amplification with liver metastasis, close follow up for liver metastasis and further clinical trials targeting CDK2 inhibitors are warranted.