Hypermethylation of tumor suppressor genes in gastric cancer: associations with demographic and clinicopathological characteristics

Binnur Bagci, Kursat Karadayi, Gokhan Bagci, Hatice Ozer, Ersin Tuncer, Ilhan Sezgin, Mustafa Turan


Background: Gastric cancer (GC) is one of the most common cancers worldwide. Despite the declining prevalence in Western countries, it is still a major health problem in Turkey and Asian countries. In the current study, we investigated the hypermethylation status of 25 TSGs in GC. Furthermore, the association between hypermethylation status of these TSGs and some demographic and clinicopathological characteristics were investigated.

Methods: Formalin-fixed paraffin-embedded tissue samples obtained from 27 patients with GC and genomic DNA isolated from these tissues. To compare the methylation status of 25 TSGs, methylation-specific multiplex ligation-dependent probe amplification (MS–MLPA) technique was used. Results were evaluated in terms of age, gender, positive lymph node status, lymphovascular invasion, perineural invasion, mortality and five-years of survival, retrospectively.

Results: Tumor suppressor gene hypermethylation was detected 16 (59.3%) of 27 GC tissues. Patients with hypermethylation-detected and patients with no hypermethylation-detected in their TSGs were classified as group 1 and group 2, respectively. The mean age of group 1 was 66.38±7.43 and the mean age of group 2 was found as 58.18±11.12 (p= 0.03). Hypermethylation was detected in 12 of 25 TSGs in patients with GC. Hypermethylation was detected as 51.8% for WT1, 40.7% for ESR1, 18.5% for CDH13, 14.8% for MSH6 and CD44, 7.4% for TP73 and PAX5 genes in the tumor tissues of patients with GC. Mean positive lymph node number was 8.81±5.38 in group 1 and 4.81±3.21 in group 2 (p= 0.037). Lymphovascular invasion, perineural invasion, mortality and five-years of mean survival were not statistically different between group 1 and group 2 (p>0.05 for all comparisons).

Conclusions: Hypermethylation frequency of certain tumor suppressor genes may increase with advancing age and with positive lymph nodes in gastric cancer patients.



Gastric cancer, Tumor suppressor gene, Hypermethylation, WT1, ESR1

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