Identification and analysis of an early diagnostic marker for malignant melanoma: ZAR1 intra-genic differential methylation

Shinojima, Yui; Terada, Tadashi; Hara, Hiroyuki; Kimura, Makoto; Igarashi, Jun; Wang, Xiaofei; Kawashima, Hiroyuki; Kobayashi, Yohnosuke; Muroi, Satomi; Hayakawa, Satoshi; Esumi, Mariko; Fujiwara, Kyoko; Ghosh, Srimoyee; Yamamoto, Tatsuo; Held, William A.; Nagase, Hiroki

doi:10.1016/j.jdermsci.2010.04.016

Cited by 29 publications

(34 citation statements)

References 16 publications

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“…Thus, ZAR1 hypermethylation is specific to few types of the ectoderm-derived tumors. Coupled with data in a previous investigation demonstrating extremely frequent hypermethylation of ZAR1 in malignant melanomas, 8) these findings suggest some overlap of pathogenesis among these tumors of presumed neural crest origin.…”

Section: Discussionsupporting

confidence: 77%

“…These frequencies were similar to that for malignant melanomas observed previously. 8) However, hypermethylation of the ZAR1 nonpromoter was by no means a universal finding in human brain tumors in general. Other common brain tumors showed infrequent ZAR1 hypermethylation: 17% of vestibular schwannomas and 33% of meningothelial meningiomas.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, hypermethylation of the off-promoter of the ZAR1 intergenic region was frequently observed in 94% of melanoma cell lines and 93% of melanoma surgical specimens, but was absent in both normal human epidermal melanocyte cell lines and melanocytic nevus surgical specimens. 8) The ZAR1 promoter regions were unmethylated in both melanoma and normal melanocytes. In part of the hypermethylated cell lines, the ZAR1 gene was over-expressed, but was either absent or extremely under-expressed in unmethylated cell lines, normal epidermal melanocyte cell lines, or fibroblast cell lines.…”

Section: Zar1 Methylation In Brain Tumorsmentioning

confidence: 99%

“…1) DNA methylation analysis with the Sequenom MassARRAY system was recently used to examine aberrant methylation in candidate human genomic regions identified through a mouse-skin cancer model study. 8) Differentially methylated regions were detected in the exon of zygote arrest 1 (Zar1 and ZAR1 in the mouse and humans, respectively) that had never been identified as an aberrant methylated region in any human tumors. Zar1 is the first identified oocyte-specific maternal-effect gene that functions during oocyte-to-embryo transition in mice.…”

Section: Zar1 Methylation In Brain Tumorsmentioning

confidence: 99%

“…The primers employed for quantitative ZAR1 methylation analysis were designed for 239 bp of the bisulfite-treated fragment for the MassARRAY EpiTYPER (Sequenom). 8) The analyzed region of ZAR1 is located 380 bp downstream from the transcription initiation site and in the middle of the first long exon. The forward primer was 5?-GGTTTTTTTTTTTAGTAGTTATTT-3?…”

Section: T Watanabe Et Almentioning

confidence: 99%

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Aberrant Hypermethylation of Non-Promoter Zygote Arrest 1 (Zar1) in Human Brain Tumors

Watanabe

Yachi

Ohta

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Zygote arrest 1 (ZAR1) is a novel maternal-effect gene which is extremely important during the oocyteto-embryo transition. Comprehensive methylation analysis of tumor-specific differentially methylated regions in human malignant melanoma has recently led to the identification of non-promoter hypermethylation of the ZAR1 gene that had never been previously linked to aberrant methylation. Strikingly, ZAR1 hypermethylation was frequently observed in melanomas but was absent in benign nevi, and ZAR1 expression was found to be up-regulated in methylated tumors. The present study searched for non-promoter ZAR1 hypermethylation in 90 primary human brain tumor samples, normal brain tissue from one autopsy case, and 7 glioma cell lines, employing Sequenom MassARRAY, in which bisulfitetreated fragments are quantitatively detected using time-of-flight mass spectroscopy. ZAR1 transcript expression levels were also evaluated by quantitative real-time reverse transcription-polymerase chain reaction in the 7 glioma cell lines. Hypermethylation of ZAR1 was frequently found in diffuse astrocytomas (7/7, 100%), anaplastic astrocytomas (16/17, 94%), glioblastomas (27/29, 93%), oligodendrogliomas (3/3, 100%), anaplastic oligodendrogliomas (3/3, 100%), and pituitary adenomas (9/10, 90%), but not in pilocytic astrocytomas (0/3). Other tumor types showed infrequent ZAR1 hypermethylation: 1 (17%) of 6 vestibular schwannomas and 4 (33%) of 12 meningothelial meningiomas. The normal brain tissue revealed no evidence of ZAR1 methylation. All 7 glioma cell lines displayed aberrant hypermethylation of ZAR1, but none had detectable ZAR1 transcript. Our findings indicate that non-promoter hypermethylation of ZAR1 is extremely frequent in diffuse gliomas and pituitary adenomas, but methylation-related aberrant ZAR1 expression is far less likely to be related to glioma tumorigenesis.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Zar1 Methylation In Brain Tumorsmentioning

confidence: 99%

Section: Zar1 Methylation In Brain Tumorsmentioning

confidence: 99%

Section: T Watanabe Et Almentioning

confidence: 99%

See 3 more Smart Citations

Aberrant Hypermethylation of Non-Promoter Zygote Arrest 1 (Zar1) in Human Brain Tumors

Watanabe

Yachi

Ohta

et al. 2010

Neurol. Med. Chir.(Tokyo)

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DNA Methylation Analysis by MALDI Mass Spectrometry

Tost

Gut

2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Genome‐wide screening of aberrant DNA methylation which associated with gene expression in mouse skin cancers

Fujiwara

Ghosh

Liang

et al. 2013

Molecular Carcinogenesis

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Epigenetic alteration of genomic DNA is a common and key process in carcinogenesis. There is considerable evidence indicating that some of the somatic alterations occurring during carcinogenesis in humans also involve the same processes as those observed in mice. Therefore, we analyzed mouse skin cancer tissues induced by the 2-stage carcinogenesis model to identify skin tumor-specific differentially methylated regions (ST-DMRs) during the multistep carcinogenesis process. We have previously identified ST-DMRs using the restriction landmark genomic scanning (RLGS) technique and reported that some of the mouse ST-DMRs were also epigenetically modified in human cancers, such as melanoma, neuroblastoma, and brain tumor. These results encouraged us to pursue global methylation screening in mouse skin carcinogenesis. Using the methylated DNA immunoprecipitation (MeDIP) method combined with the NimbleGen promoter plus CpG island (CpGi) array, we identified 615 ST-DMRs. In combination with global gene expression analysis, 91 of these ST-DMRs were shown to be located on or around the genes differentially expressed between normal skin and tumor tissues, including a candidate human tumor suppressor gene Tfap2e. As observed in human colorectal cancers, Tfap2e was methylated at a CpGi located in intron 3 and downregulated in skin tumors. Our results identified aberrant methylated regions that were associated with gene expression regulation during carcinogenesis, which may indicate critical genetic regions also involved in human carcinogenesis. © 2013 Wiley Periodicals, Inc.

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Identification and analysis of an early diagnostic marker for malignant melanoma: ZAR1 intra-genic differential methylation

Cited by 29 publications

References 16 publications

Aberrant Hypermethylation of Non-Promoter Zygote Arrest 1 (Zar1) in Human Brain Tumors

Aberrant Hypermethylation of Non-Promoter Zygote Arrest 1 (Zar1) in Human Brain Tumors

DNA Methylation Analysis by MALDI Mass Spectrometry

Genome‐wide screening of aberrant DNA methylation which associated with gene expression in mouse skin cancers

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