ArticleCellular oncology (Dordrecht, Netherlands)2014
Somatic mutations of amino acid metabolism-related genes in gastric and colorectal cancers and their regional heterogeneity--a short report.
Article in Cellular oncology (Dordrecht, Netherlands), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 65 citations in OpenAlex.
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- Metabolic pathway-based molecular subtyping of colon cancer reveals clinical immunotherapy potential and prognosis.Journal of cancer research and clinical oncology · 2023Article
- DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Weighted gene co-expression network analysis reveals key genes involved in pancreatic ductal adenocarcinoma development.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Inactivation of the LKB1-AMPK signaling pathway does not contribute to salivary gland tumor development - a short report.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Consensus reference gene(s) for gene expression studies in human cancers: end of the tunnel visible?Cellular oncology (Dordrecht, Netherlands) · 2015Review
- Manipulation of tumor metabolism for therapeutic approaches: ovarian cancer-derived cell lines as a model system.Cellular oncology (Dordrecht, Netherlands) · 2015Article
- Two Loops Undergoing Concerted Dynamics Regulate the Activity of the ASH1L Histone Methyltransferase.Biochemistry · 2015Article
- Genetic polymorphism in DNMTs and gastric cancer: A systematic review and meta-analysis.Porto biomedical journalArticle
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4 authors at 1 institution in 1 country.
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Abstract
backgroundMetabolic reprogramming is an emerging topic in cancer research. However, genetic alterations in genes encoding enzymes involved in amino acid metabolism are largely unknown. The aim of this study was to explore whether genes known to be involved in amino acid metabolism are mutated in gastric cancer (GC) and/or colorectal cancer (CRC).
methodsThrough a public database search, we found that a number of genes known to be involved in amino acid metabolism, i.e., AGXT, ALDH2, APIP, MTR, DNMT1, ASH1L, ASPA, CAD, DDC, GCDH, DLD, LAP3, MCEE and MUT, harbor mononucleotide repeats that may serve as mutation targets in cancers exhibiting microsatellite instability (MSI). We assessed these genes for the presence of the mutations in 79 GCs and 124 CRCs using single-strand conformation polymorphism (SSCP) and direct sequencing analyses.
resultsUsing SSCP in conjunction with DNA sequencing we detected frameshift mutations in AGXT (17 cases), ALDH2 (3 cases), APIP (4 cases), MTR (5 cases), DNMT1 (1 case), ASH1L (1 case), ASPA (2 cases), CAD (2 cases), DDC (1 case), GCDH (3 cases), DLD (1 case), LAP3 (1 case), MCEE (5 cases) and MUT (1 case). These mutations were exclusively detected in MSI-high (MSI-H), and not in MSI-low or MSI-stable (MSI-L/MSS) cases. In addition, we analyzed 16 CRCs for the presence of intra-tumor heterogeneity (ITH) and found that two CRCs harbored regional ITH for GCDH frameshift mutations.
conclusionsOur data indicate that genes known to be involved in amino acid metabolism recurrently acquire somatic mutations in MSH-H GCs and MSH-H CRCs and that, in addition, mutation ITH does occur in at least some of these tumors. Together, these data suggest that metabolic reprogramming may play a role in the etiology of MSI-H GCs and CRCs. Our data also suggest that ultra-regional mutation analysis is required for a more comprehensive evaluation of the mutation status in these tumors.
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