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Gene Expression and Methylation Analysis in Melanomas and Melanocytes From the Same Patient: Loss of NPM2 Expression Is a Potential Immunohistochemical Marker for Melanoma
- Source :
- Frontiers in Oncology, Frontiers in Oncology, Vol 8 (2019)
- Publication Year :
- 2018
-
Abstract
- DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. In order to compare the methylation status in melanoma tissues and melanocytes from the same individuals, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports. In many normal melanocytes, NPM2 showed distinct immunohistochemical staining, while its expression was lost in malignant melanoma cells. In particular, intraepithelial lesions of malignant melanoma, an important challenge in clinical practice, could be distinguished from benign nevi. The present findings indicate the importance of using fresh melanoma samples, not melanoma cell lines and melanocytes in epigenetic studies. In addition, NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease.
- Subjects :
- 0301 basic medicine
Cancer Research
melanocyte
Melanocyte
Biology
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Gene expression
medicine
melanoma
Epigenetics
neoplasms
Original Research
epigenetics
Melanoma
NPM2
Cancer
Methylation
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
DNA methylation
nevi
Cancer research
Immunohistochemistry
methylation
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in oncology
- Accession number :
- edsair.doi.dedup.....41fae3ba2ec409c1b4e47b77aa516b0e