Modal variety of microsatellite instability in human endometrial carcinomas

Eto, Takako; Zhao, Yan; Maruyama, Akiko; Miyashita, Kaname; Yasui, Aiko; Nakao, Seiki; Taguchi, Kenichi; Shimokawa, Mototsugu; Oda, Shinya; Saito, Toshiaki

doi:10.1007/s00432-015-2030-2

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…As previously reported 22 , 25 , 43 , 49 , the following five microsatellite loci on chromosomes were examined for MSI based on the revised Bethesda panel 48 – 50 : BAT26, BAT25, D2S123, D5S346, and D17S250. MSI status was judged according to previous reports 43 , 49 , 51 , 52 (Supplementary Fig. S5 ).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

Michigami

Watari

Ito

et al. 2018

Sci Rep

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The risk of gastric cancer (GC) remains in precancerous conditions, including atrophic mucosa and intestinal mucosa (IM), even after H. pylori treatment. To define the molecular changes following H. pylori eradication, molecular alterations in the gastric mucosa with and without GC were evaluated in a long-term follow-up study. A total of 232 biopsy specimens from 78 consecutive patients, including atrophic gastritis patients with follow-up ≥3 y after successful H. pylori eradication (AG group), patients who developed early GC after successful eradication (≥3 y) (GC group), and patients with H. pylori-positive atrophic gastritis (Hp group), were analyzed. H. pylori eradication was associated with significant reductions of methylation of several genes/loci in atrophic mucosa (non-IM), but not in IM. In contrast, the incidence of CpG island methylator phenotype (CIMP) in IM was significantly higher in the GC group than in the AG group. miR-124a-3 methylation and miR-34c methylation were more frequently identified in IM, with very few in non-IM mucosa among the three groups. H. pylori eradication can reverse methylation only in non-IM mucosa. CIMP in IM may have potential as a surrogate maker of GC development, and methylation of miR-124a-3 and miR-34c is a molecular event in IM that may not be associated with GC development.

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Section: Patients Materials and Methodsmentioning

confidence: 99%

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

Michigami

Watari

Ito

et al. 2018

Sci Rep

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“…4.0 (Applied Biosystems). The MSI status was judged according to previous reports 40 , 53 , 54 (Supplementary Fig. S2 ).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…S2 ). In cases that were indistinguishable between MSI and loss of heterozygosity 54 , the allelic imbalance (AI) ratio was calculated. MSI was determined to be positive when the AI ratio (normal allele 1:normal allele 2/tumor allele 1:tumor allele 2) was <0.67 or >1.35, as previously reported 40 , 53 (Supplementary Fig.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer

Michigami

Watari

Ito

et al. 2017

Sci Rep

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The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95% CI: 0.06-0.41, p = 0.0002), but was less effective in reversing the methylation that occurred in IM. Frequent hypermethylation including that of CDH1 in AM increased in the GC group compared to the AG group, and CDH1 methylation was an independent predictive marker of GC (OR: 8.50, 95% CI: 2.64-25.33, p = 0.0003). In patients with long-term aspirin use, the changes of molecular events in AM but not IM may be an important factor in the reduction of cancer incidence. In addition, methylation of the CDH1 gene in AM may be a surrogate of GC.Helicobacter pylori (H. pylori) infection causes non-atrophic gastritis, which progresses to atrophic gastritis, intestinal metaplasia (IM), dysplasia, and finally, gastric cancer (GC) 1 . Thus, the International Agency for Research on Cancer has concluded that H. pylori is a class I human carcinogen 2 . To date, some meta-analyses have shown that H. pylori eradication reduced the risk of GC in patients with chronic gastritis who underwent endoscopic resection (ER) for early GC 3-7 . However, a recent study from Japan showed that even after H. pylori infection was cured and gastric inflammation was eliminated, there was still a risk of GC in the long-term 8 . Additionally, metachronous GC occurred to some degree in patients who had H. pylori infection eradicated following ER for early GC 9-13 . Thus, it remains controversial if H. pylori eradication suppresses the development of GC. To reduce the risk of GC after H. pylori eradication, other combination treatments such as anti-inflammatory agents and dietary or nutritional intervention are needed.Some studies including meta-analyses have reported that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a reduced risk of both colorectal cancer and GC [14][15][16][17] . Their anti-carcinogenetic effects have been attributed to inhibition of the cyclooxygenase pathway and their anti-inflammatory abilities 18,19 . The roles of a number of genetic and epigenetic alterations, including microsatellite instability (MSI) and promoter hypermethylation of multiple tumor-related genes, are reportedly involved in GC and precancerous conditions of the stomach [20][21][22][23][24][25][26][27][28][29][30][31][32][33] . The CpG island methylator phenotype (CIMP), characterized by extensive

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“…MMR genes may be abnormally methylated and cancer develops when MSI occurs in regions of tumor suppressor genes. Numerous microsatellites are detectable by PCR and are found in 20-40% of cases of endometrial cancer (22,(55)(56)(57). Genes involved in the MMR system include hMLH1, MutS protein homolog 2 (hMSH2) and hMSH6, and postmeiotic segregation increased 2 (hPMS2) is frequently abnormally methylated (56).…”

Section: Diagnosis Of Endometrial Cancer and Epigenetic Abnormalitiesmentioning

confidence: 99%

Recent findings on epigenetic gene abnormalities involved in uterine cancer

Yanokura

Banno

Kobayashi

et al. 2017

Molecular and Clinical Oncology

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Abstract. Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress. These include the evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at lower levels compared with those in normal tissues, as a prognostic marker in cervical cancer; combination therapy with 5-azacytidine and cisplatin; combination treatment focusing on tumor necrosis factor-related apoptosis-inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in endometrial cancer; and use of a demethylating agent to reactivate tumor suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes using biomarkers may be used for histological classification, evaluation of disease progression and identification of compounds that are able to modulate epigenetic changes and may be useful for uterine cancer treatment.

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Modal variety of microsatellite instability in human endometrial carcinomas

Cited by 11 publications

References 35 publications

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer

Recent findings on epigenetic gene abnormalities involved in uterine cancer

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