Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.

Automated summary

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer with high mortality rate. Research suggests that HAS may originate from pluripotent precursor cells and has high stemness and methionine cycle activity. Genes involved in the methionine cycle, such as MAT2A and AHCY, are potential targets for HAS treatment.