Multi-regional sequencing reveals the genetic and immune heterogeneity of non-cancerous tissues in gastric cancer

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

3 Scopus Citations
View graph of relations

Author(s)

  • Shen Li
  • Yingqi Hu
  • Xiao Xu
  • Jiantao Cui
  • Ziyu Li
  • Jiafu Ji
  • Rui Xing

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)454-465
Journal / PublicationJournal of Pathology
Volume263
Issue number4-5
Online published6 Jun 2024
Publication statusPublished - Aug 2024

Abstract

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.

Research Area(s)

  • evolution, gastric cancer, mutational signature, NAT, tumor immunity

Citation Format(s)

Multi-regional sequencing reveals the genetic and immune heterogeneity of non-cancerous tissues in gastric cancer. / Zhou, Yong; Li, Shen; Hu, Yingqi et al.
In: Journal of Pathology, Vol. 263, No. 4-5, 08.2024, p. 454-465.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review