Mutations in Epigenetic Regulation Genes in Gastric Cancer
| Autor: | Vladimir V Strelnikov, Alexander S Tanas, Dmitry S. Mikhaylenko, T. V. Khorobrykh, Marina V. Nemtsova, Ekaterina B. Kuznetsova, Irina V. Bure, A.I. Kalinkin, Ekaterina A. Alekseeva, I. I. Bykov |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Signet ring cell Somatic cell gastric cancer Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens Biology medicine.disease Article Chromatin remodeling Histone Oncology DNA methylation Cancer research medicine biology.protein somatic mutations Epigenetics molecular genetic markers Gene epigenetic regulation genes RC254-282 |
| Zdroj: | Cancers, Vol 13, Iss 4586, p 4586 (2021) Cancers Volume 13 Issue 18 |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary Epigenetic mechanisms, such as DNA methylation/demethylation, covalent modifications of histone proteins, and chromatin remodeling, create specific patterns of gene expression. Epigenetic deregulations are associated with oncogenesis, relapse of the disease and metastases, and can serve as a useful clinical marker. We assessed the clinical relevance of integrity of the genes coding for epigenetic regulator proteins by mutational profiling of 25 genes in 135 gastric cancer (GC) samples. Overall, mutations in the epigenetic regulation genes were found to be significantly associated with reduced overall survival of patients in the group with metastases and in the group with tumors with signet ring cells. We have also discovered mutual exclusivity of somatic mutations in the KMT2D, KMT2C, ARID1A, and CHD7 genes in our cohort. Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts. Abstract We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts. |
| Databáze: | OpenAIRE |
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