DNA methyltransferases 1, 3a, and 3b overexpression and clinical significance in gastroenteropancreatic neuroendocrine tumors

Rahman, Mustafizur; Qian, Zhi Rong; Wang, Elaine Lu; Yoshimoto, Katsuhiko; Nakasono, Masahiko; Sultana, Razia; Yoshida, Tomoyuki; Hayashi, Toshitetsu; Haba, Reiji; Ishida, Mitsuaki; Okabe, Hidetoshi; Sendo, Toshiaki

doi:10.1016/j.humpath.2010.01.011

Cited by 41 publications

(30 citation statements)

References 44 publications

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“…In addition, the over-expression of DNMT3a mRNA and protein were detected in various cancers including GC, these results revealed that increased DNMT3a expressiom may play a role in tumorgenesis of GC (Oh et al, 2007;Ding et al, 2008;Rahman et al, 2010;He et al, 2011;Yang et al, 2011). However, no differences of DNMT3a expression was detected between different genotype carriers in GC patients in our study.…”

Section: Discussionmentioning

confidence: 91%

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Cao

Jia²,

Cao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 91%

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Cao

Jia²,

Cao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…However, DNMT3a overexpression was also found to be associated with tumor aggressively in other types of cancers. Indeed, a significant correlation between DNMT3a protein expression and higher tumor stage was reported in gastroenteropancreatic neuroendocrine tumors [11]. Moreover, a poorer recurrence-free survival was noted in hepatocarcinomas with increased DNMT3a mRNA [12].…”

Section: Discussionmentioning

confidence: 98%

“…Using semiquantitative reverse transcription-PCR, Chen et al [9] have demonstrated that DNMT1 overexpression in ovarian epithelial cancers was correlated with low tumor differentiation, advanced clinical stage, and lymphatic metastasis. By using immunohistochemistry, a significant correlation was reported between DNMT1 overexpression and higher-stage tumors in 63 gastroenteropancreatic neuroendocrine tumors, suggesting that the overexpression of DNMT1 was related to tumorigenesis and progression of these tumors [11]. However, given the limited studies exploring the DNMT1 expression in breast cancer, further research is required to better elucidate the precise clinical significance of DNMT1 expression in this cancer.…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers

et al. 2012

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Summary DNA methyltransferase 1, 3a, and 3b affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. The current study was designed to analyze DNA methyltransferase expression by immunohistochemistry in a series of 94 Tunisian sporadic breast carcinomas. Results were correlated to clinicopathologic parameters and promoter methylation status of 8 tumor suppressor genes (BRCA1, BRCA2, RASSFA1, TIMP3, CDH1, P16, RARβ2, and DAPK). Overexpression of DNA methyltransferase 1, 3a, and 3b was detected in 46.8%, 32%, and 44.7% of cases, respectively. A significant correlation was found between DNA methyltransferase 1 overexpression and Scarff-Bloom-Richardson histologic grade III (P = .01). DNA methyltransferase 3a overexpression was significantly associated with menopausal status (P = .01), Scarff-Bloom-Richardson histologic grade III (P = .0001), estrogen (P = .04) and progesterone (P = .007) receptor negativity, and HER2 overexpression (P = .004). However, DNA methyltransferase 3a overexpression was found less frequently in the luminal A intrinsic breast cancer subtype (9.7%) than in luminal B (53%), HER2 (41%), and triple-negative (50%) subtypes (P = .001). DNA methyltransferase 3b overexpression shows significant correlation with promoter hypermethylation of BRCA1 (P = .03) and RASSFA1 (P = .04) and with the hypermethylator phenotype (more than 4 methylated genes, P = .01). These data suggest that overexpression of various DNA methyltransferases might represent a critical event responsible for the epigenetic inactivation of multiple tumor suppressor genes, leading to the development of aggressive forms of sporadic breast cancer.

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“…DNA methylation at RASSF1A was correlated to worse prognosis in NETs (122,123). Rather than having K-RAS or BRAF mutations, well differentiated NETs have methylation in RASSF1A gene, observed in pancreatic, pulmonary and gastrointestinal tumors (122,123). MEN1 and Daxx/ATRX are part of chromatin modifying complexes the most frequently mutated genes in NETs and mutations of menin and Daxx/ATRX are not mutually exclusive in the same tumor.…”

Section: Epigenetics In Neuroendocrine Tumorsmentioning

confidence: 99%

Molecular challenges of neuroendocrine tumors (Review)

Patel

Galoian

2017

Oncol Lett

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Abstract. Neuroendocrine tumors (NETs) are a very heterogeneous group that are thought to originate from the cells of the endocrine and nervous systems. These tumors develop in a number of organs, predominantly in the gastrointestinal and pulmonary systems. Clinical detection and diagnosis are reliable at the late stages when metastatic spread has occurred. However, traditional conventional therapies such as radiation and chemotherapy are not effective. In the majority of cases even surgical resection at that stage is unlikely to produce promising reusults. NETs present a serious clinical challenge, as the survival rates remain low, and as these rare tumors are very difficult to study, novel approaches and therapies are required. This review will highlight the important points of accumulated knowledge covering the molecular aspects of the role of neuroendocrine cells, hormonal peptides, the reasons for ectopic hormone production in NET, neuropeptides and epigenetic regulation as well as the other challenging questions that require further understanding.

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DNA methyltransferases 1, 3a, and 3b overexpression and clinical significance in gastroenteropancreatic neuroendocrine tumors

Cited by 41 publications

References 44 publications

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers

Molecular challenges of neuroendocrine tumors (Review)

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