Genomic alterations and clinical correlations of Chinese patients with hepatoid adenocarcinoma of the stomach/alpha-fetoprotein gastric cancer

e13514 Background: Hepatoid adenocarcinoma of stomach (HAS) is a rare subtype of gastric cancer (GC) with poor prognosis due to frequent liver metastasis. HAS, recognized as an extrahepatic cancer that resembles hepatocellular carcinoma (HCC), is characterized by solid sheet-like growth structures with hepatoid differentiation and excessive production of alpha-fetoprotein (AFP). This HAS subtype of GC (AFPGC) is genetically distinct compared to other common GC but requires more evidences for better characterization. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were collected from 25 HAS and 9 AFPGC patients at Zhongshan Hospital from July 2013 to August 2017 for whole exome sequencing (WES) test. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: Our cohort included 25 males and 9 females who had undergone surgical treatment. The 25 HAS patients had a median age of 66.5 years (range 48-82) and the 9 AFPGC patients had a median age of 64 years (range 52-76). Patients with AFP>20 had a significantly better overall survival (OS) compared with patients with AFP≤20. The most frequently mutated genes were TP53 (44%), TTN (44%), and MUC19 (30%) in HAS tumor samples and CDC27 (44%), NKX2-3 (44%), and TTN (44%) in AFPGC samples. Patients with URI1 or POP4 alterations had a significantly poorer OS than patients without those genes mutations (7.6 months vs. 19.8 months, p = 0.016, and 10.9 months vs. 19.7 months, p = 0.038, respectively). However, patients with SPTA1 alterations had a significantly better OS compared to patients without SPTA1 alterations (27.6 months vs. 15.8 months, p = 0.042). Patients with higher tumor mutational burden (TMB) (≥3.9 muts/Mb) had a significantly better OS compared with patients with lower TMB (