Differences in the genetic landscape of primary gastric adenocarcinoma and its regional lymph node metastases

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Abstract

Introduction. Lymphogenous metastasis is a key stage in the progression of gastric cancer. The practice of personalized treatment has historically been based on histological and molecular analysis of the primary tumor, while the molecular-genetic landscape of the metastatic focus may differ significantly, and sometimes radically.

The purpose of this review is to summarize and analyze current data on the nature and extent of genetic differences between primary gastric adenocarcinoma and its synchronous or metachronous metastases to regional lymph nodes.

Material and methods. Full-text publications from the PubMed and eLibrary electronic databases were selected for analysis. The search covered a period of 15 years.

Results. The study examines aspects of intratumoral heterogeneity, discordance in the status of key driver mutations (TP53, CDH1, ARID1A, ERBB2), variability in genomic instability patterns (CIN, MSI, EBV), as well as differences in signaling pathways and gene expression profiles. Particular attention is paid to the mechanisms underlying these changes (clonal selection, ongoing genomic instability, adaptation to the microenvironment, and the influence of therapy). Based on the analysis, practical conclusions for clinical oncology are formulated.

Conclusion. Metastases of gastric cancer in regional lymph nodes are the result of a multistage process of clonal selection and evolution, leading to the formation of unique genetic, epigenetic, and transcriptomic landscapes. This highlights the need to rethink current approaches to biopsy, biomarker testing, and therapeutic response monitoring, with an emphasis on the potential role of metastatic site analysis and liquid biopsy.

About the authors

Anatoly A. Ivanov

Federal State Budgetary Scientific Institution “Federal Research Center for Fundamental and Translational Medicine”

Author for correspondence.
Email: anatolij0199@yandex.ru
ORCID iD: 0000-0001-5040-8854

Senior Researcher, Candidate of Medical Sciences, Institute of Molecular Pathology and Pathomorphology

Russian Federation, Timakova str., 2, Novosibirsk, 630060

Ashot M. Avdalyan

State Budgetary Healthcare Institution “Moscow Multidisciplinary Clinical Center "Kommunarka" of the Moscow City Health Department”; Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation

Email: ashot_avdalyan@mail.ru
ORCID iD: 0000-0002-2229-1713

Professor of the Department of Pathological Anatomy, Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, Head of the Pathology Department, Moscow Multidisciplinary Clinical Center “Kommunarka” of the Moscow City Health Department. Doctor of Medical Sciences

Russian Federation, Sosensky Stan str., 8, build. 3, Kommunarka settlement, Moscow, 108814; Dolgorukovskaya str., 4, Moscow, 127006

Maksim A. Bakarev

Federal State Budgetary Scientific Institution “Federal Research Center for Fundamental and Translational Medicine”

Email: mabakarev@frcftm.ru
ORCID iD: 0000-0002-9614-592X

Chief Researcher, Institute of Molecular Pathology and Pathomorphology, Doctor of Medical Sciences, Professor

Russian Federation, Timakova str., 2, Novosibirsk, 63006

Elena L. Lushnikova

Federal State Budgetary Scientific Institution “Federal Research Center for Fundamental and Translational Medicine”

Email: pathol@inbox.ru
ORCID iD: 0000-0002-3269-2465

Chief Researcher, Institute of Molecular Pathology and Pathomorphology, Doctor of Biological Sciences, Professor

Russian Federation, Timakova str., 2, Novosibirsk, 63006

Maria B. Rumyantseva

State Budgetary Healthcare Institution “Moscow Multidisciplinary Clinical Center "Kommunarka" of the Moscow City Health Department”

Email: docrum83@gmail.ru
ORCID iD: 0009-0004-4546-8501

Pathologist at the Pathology Department

Russian Federation, Sosensky Stan str., 8, build. 3, Kommunarka settlement, Moscow, 108814

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