Histone Methyltransferases Useful in Gastric Cancer Research

Abstract

Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients’ clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3, and EHMT2 genes. The PRDM9 gene is among most mutated and amplified HMTs within the data set studied. PRDM14 is downregulated in 79% of the samples and the SUV39H2 gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.

PRDM12 in Health and Diseases

“…These findings indicated that PRDM12 expression level alterations in prostate cancer tissue samples could have a prognostic value [ 69 ]. Similarly, in a recent study, somatic copy number alterations were also found for PRDM12 in stomach adenocarcinoma samples [ 70 ]. However, currently, no studies have identified the mechanism by which PRDM12 could participate in oncogenesis.…”

SMYD Family Members Serve as Potential Prognostic Markers and Correlate with Immune Infiltrates in Gastric Cancer

“…In colon and lung cancer cells, SMYD5 maintains chromosomal integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during cell differentiation [ 60 ]. SMYD5 is differentially expressed in GC, indicating that it is a potential marker for diagnosis and prognosis [ 19 , 20 ]. By constructing the SMYD-based signature and nomogram model, we confirmed that SMYDs are closely related to GC prognosis and are thus potential prognostic markers.…”

“…Additionally, high SMYD3 expression is associated with poor prognosis [ 16 , 17 ]. SMYD4 has been identified as a tumor suppressor gene in breast cancer [ 18 ], and SMYD5 may be involved in cancer and stem cell maintenance [ 19 , 20 ]. Finally, several studies have suggested the association of SMYDs with immune infiltration in breast cancer and digestive system malignancies [ 21 , 22 ].…”

A Computational Approach to Predict the Role of Genetic Alterations in Methyltransferase Histones Genes With Implications in Liver Cancer

“…32,33 Recent evidence shows that the aberrant activity of HMTs, due to amplification, deletion, or mutation of their corresponding genes, contributes to the initiation and progression of cancer. 8,13,33 Consequently, a promising strategy could target populations of patients who are carriers of these alterations. For years, it has been known that different types of cancer share common molecular mechanisms whose dysfunction allows uncontrolled cell proliferation through the deregulation or mutation of genes that positively or negatively influence the regulation of cell proliferation, migration and differentiation.…”