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Molecular genetic alterations in mucosa of gastric cancer patients after subtotal distal gastrectomy

Keywords:

N.V. Checunova – Post-graduate Student, Faculty Surgery Department No 1, Medical Faculty in I.M. Sechenov First Medical State University» of the Russian Ministry of Health
I.I. Bykov – Ph.D. (Med.), Faculty Surgery Department No 1, Medical Faculty in I.M. Sechenov First Medical State University» of the Russian Ministry of Health
T.V. Kchorobrich – Dr.Sc. (Med.), Professor, Faculty Surgery Department No 1, Medical Faculty in I.M.Sechenov First Medical State University» of the Russian Ministry of Health
M.V. Nemtsova – Dr.Sc. (Biol.), Professor of laboratory of human molecular genetics of Research Institute of Molecular Medicine in I.M. Sechenov First Medical State University» of the Russian Ministry of Health, Professor of the of the Department of Medical Genetics in Russian Medical Academy of Postgraduate Educations of the Russian Ministry of Health. E-mail: nemtsova_m_v@mail.ru


Epigenetic silencing of tumor-related genes, due to hypermethylation of the CpG sites in the promoter regions, has emerged as one of the main genetic alterations in gastric cancer development. We investigated the clinical and prognostic importance of CpG-island hypermethylation in 6 tumor-related genes (CDH1, RASSF1А, MLH1, N33, DAPK, RUNX,) for gastric cancer patients. We examined hypermethylation of 6 tumor-related genes in 40 frozen biopsies of the gastric mucosa, obtained during endoscopic research, from patients pre-treated with surgery on gastric cancer (6 to 39 mounth before). There was no hypermethylation of the genes in 31/40 biopsies (meth-). In 9/40 samples, we have identified aberrant methylation of CDH, N33, RUNX3 genes (meth+), in 2 patient we have identified aberrant methylation of three genes (CDH1, N33, RUNX3), in 2 patients – two genes (CDH1, N33), in 5 patients - of one methylated gene (N33 or RUNX3 or CDH1). We have shown significant association of aberrant methylation of CDH1, N33, RUNX3 genes in patients (meth+) with distant metastases (p=0,0462), generalization of the tumor process (p=0,029) and presence of chronic gastritis and gastric ulcer (p=0,0077). The current study shows that the hypermethylation of tumor-related genes may be used as additional marker for postsurgical monitoring of gastric cancer patients.
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