Cancer Res Treat.  2016 Apr;48(2):853-858. 10.4143/crt.2014.356.

PTEN Methylation Dependent Sinonasal Mucosal Melanoma

• Lee SH
• Roh MR
• Kang B
• Park KH
• Kim SH
• Lee SE
• Rha SY

• KMID: 2454366
• DOI: http://doi.org/10.4143/crt.2014.356

Abstract

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

Keyword

Methylation; Phosphatase and tensin homolog; Sinonasal melanoma

MeSH Terms

Carcinogenesis
CpG Islands
Epigenomics
Liver
Melanoma*
Methylation*
Neoplasm Metastasis
Phosphatidylinositols
Phosphatidylinositols

Figure

• 

  Fig. 1. Imaging analysis of the patient. (A) Magnetic resonance imaging (MRI) of the paranasal sinuses shows an enhancing soft tissue lesion in the left frontoethmoid sinus extending to the left orbit. (B, C) Multiple metastases are seen in liver and vertebrae in the abdominopelvic computed tomography and spine MRI scan.

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  Fig. 2. Pathologic findings of the biopsy specimen obtained from the nasal cavity mass. (A) Round tumor cells with atypia, showing pleomorphic and hyperchromatic nuclei with prominent nucleoli are seen (H&E staining, ×400). (B-D) Immunohistochemistry staining shows positive staining in the tumor cells for S-100 (B) and Melan A (C) (B and C, ×200), and decreased level of PTEN protein expression (D, ×200).

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  Fig. 3. Examination of PTEN polymerase chain reaction (PCR) product and methylation status of PTEN promoter gene. (A) Agarose gel electrophoresis shows loss of PTEN PCR product in the SK-MEL-24 cell line, which is known to have PTEN deletion, while the patient sample shows a band of PTEN product. (B) Methylation status of the PTEN promoter examined by pyrosequencing using bisulfite-modified DNA shows methylation of five different CpG island sites in the patient’s genomic DNA.

Reference

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