Aberrant MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation in choroid plexus tumors

Hasselblatt, Martin; Mühlisch, Jörg; Wrede, Brigitte; Kallinger, Birgit; Jeibmann, Astrid; Peters, Ove A.; Kutluk, Tezer; Wolff, Johannes; Paulus, Werner; Frühwald, Michael C.

doi:10.1007/s11060-008-9694-2

Cited by 16 publications

(7 citation statements)

References 25 publications

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“… 28 , 29) It has been reported that the combined bisulfite restriction analysis confirmed over 10% methylation of CpGs 17 and 31 in 58% of CPTs. 30) In our study, immunohistochemical expression of MGMT was negative (< 10% of neoplastic cells) in 1 (10%) of 10 cases. The efficacy of Temozolomide for CPTs and its relation with MGMT methylation is to be elucidated.…”

Section: Discussionmentioning

confidence: 41%

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases

Bohara¹,

Hirabaru²,

Shimizu³

et al. 2015

Neurol. Med. Chir.(Tokyo)

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Choroid plexus tumors (CPTs) are rare intraventricular neoplasms accounting for about 0.3–0.6% of all intracranial tumors. This retrospective study on CPTs presents clinico-pathological features and management strategies based on a 20-year single-institutional experience. This series included 10 consecutive patients with pathologically proven CPTs; 5 choroid plexus papillomas (CPPs), 3 atypical CPPs (ACPPs), and 2 choroid plexus carcinomas (CPCs). Their clinical, radiological, and histopathological features as well as management including follow-up studies were reviewed. The patients included five males and five females, aging from 0 years to 61 years with median of 28 years. The affected site was lateral ventricle in two adults and fourth ventricle in eight patients; four children and four adults. The most common symptoms were gait disturbance and memory disturbance. All the patients underwent craniotomy with total, subtotal, and partial removals achieved in 50%, 40%, and 10% of the patients, respectively. The occurrence of the high grade subtypes was 50% in both the adult and pediatric groups. The Ki-67/MIB-1 index increased across the three histological subtypes, from CPP to ACPP and then to CPC. Adjuvant therapy was administered in three patients. The two patients (one adult and one child) with CPC died of whole central nervous system dissemination. At a median of 62-month follow-up, the other eight patients were alive, with only one patient having recurrence and reoperation. The results demonstrate that gross total resection is usually curative for CPP and ACPP, and adjuvant chemoradiotherapy would be required for CPC and incompletely resected ACPP.

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Section: Discussionmentioning

confidence: 41%

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases

Bohara¹,

Hirabaru²,

Shimizu³

et al. 2015

Neurol. Med. Chir.(Tokyo)

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“…However, these cases received temozolomide chemotherapy without analysis of MGMT promoter methylation. Hasselblatt et al [15] reported that aberrant methylation of MGMT promoter was confirmed in seven of eight cases in CPC without evaluation of the temozolomide efficacy. Our case may be rare with lack of methylation of the MGMT promoter.…”

Section: Discussionmentioning

confidence: 99%

“…The DNA-alkylating agent temozolomide is effective for malignant gliomas, whereas evidence for its efficacy for CPT remains unclear [7,[12][13][14]. Promoter methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) DNA-repair gene is a marker for the response to alkylating agents in malignant gliomas, although this has not been probed in CPT [13][14][15]. Herein, we report an adult case of CPC with craniospinal seeding who underwent subtotal resection followed by administration of temozolomide with assessment of MGMT promoter methylation status.…”

Section: Introductionmentioning

confidence: 99%

MGMT promoter methylation and temozolomide response in choroid plexus carcinoma

et al. 2011

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Choroid plexus carcinoma (CPC) is a malignant tumor with a strong tendency to spread along the cerebrospinal fluid pathway. There is no standardized chemotherapy protocol for this rare tumor. We report a 38-year-old man with CPC in the lateral ventricle with obstructive hydrocephalus. Because of the poor demarcation between thalamus and fornix, subtotal tumor resection was performed. Postoperative spine magnetic resonance (MR) image revealed whole spinal axis dissemination. After diagnosis of CPC, the patient was treated with whole ventricular and spine radiation concomitant with temozolomide chemotherapy, although the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated. Although MR images revealed transient stable disease during adjuvant therapy, tumor progression was depicted after four cycles of temozolomide therapy. We discuss the ineffectiveness of adjuvant temozolomide therapy for CPC in connection with O 6 -methylguanine-DNA methyltransferase promoter methylation.

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“…However, the percentage of methylation (10%) was lower than those reported in other tumors, including liver carcinoma (12.4% to 58%) [33][34][35][36][37][38][39][40][41][42][43][44]. One explanation might be that workers were in the chromosome damage stage, which is an early effect of VCM exposure.…”

Section: S H O R T C O M M U N I C a T I O N F Wu Et Al Ijomeh 2013mentioning

confidence: 95%

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

Wu¹,

Liu²,

Qiu³

et al. 2013

International Journal of Occupational Medicine and Environmental Health

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Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM). Materials and Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups. Results: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05). Conclusions: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study. inactivation of tumor suppressor genes in human cancers. Several investigators have reported that CpG islands on the promoters of the MGMT and hMLH1 genes are hypermethylated in several malignancies and aberrant hypermethylation represses the expression of MGMT and hMLH1 [17][18][19][20]. A high frequency of p16 hypermethylationin was observed in vinyl chloride (VC)-associated hepatocellular carcinomas (HCC) [21]. Aberrant methylation of tumor suppressor genes might also act in the early stages of the multistep process of carcinogenesis [22]. Based on the information above, we hypothesized that epigenetic silencing of MGMT and hMLH1, by promoter hypermethylation, might be involved in VCM-exposureinduced chromosome damage which is the early stage in the process of liver angiosarcoma. In the present study, we attempted to identify the MGMT and hMLH1 promoter methylation status in genomic DNA isolated from peripheral blood lymphocytes from workers exposed to VCM using a methylation-specific polymerase chain reaction (MS-PCR) and to analyze the correlation between MGMT and hMLH1 gene promoter methylation and chromosome damage induced by VCM exposure. MATERIALS AND METHODS Study populationWorkers employed in a VCM polymerization plant in China were studied. Prior to the study, written informed consent had been obtained from each subject and a standardized questionnaire had been used to obtain personal information, smoking and alcohol habits, medication and occupational history. The subjects exposed to VCM for longer than one year were selected if the following criteria were met: detailed questionnaires had been completed, the CBMN test results and a blood sample had been provided and the MSP analysis for the MGMT and hMLH1 genes was completed successfully. A total of 101 workers met these criteria. Individuals who smoked once a day for

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Aberrant MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation in choroid plexus tumors

Cited by 16 publications

References 25 publications

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases

MGMT promoter methylation and temozolomide response in choroid plexus carcinoma

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

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