Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells

BACKGROUND: We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAF V600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. METHODS: To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAF V600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. RESULTS: First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. CONCLUSION: Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

Retrospective study of canine cutaneous tumors in Korea

Over the 42 month period from January 2003 to June2006, a total of 2,952 canine biopsy specimens werereceived from the Veterinary Medical Teaching Hospitalof Seoul National University and from veterinary practitionersacross the nation. Out of these, 748 (25.34%) cases werediagnosed as canine cutaneous tumors in the Departmentof Veterinary Pathology, College of Veterinary Medicine,Seoul National University, Korea. Thirty-eight differenttypes of cutaneous tumors were identified and categorizedinto epithelial and melanocytic tumors (56.95%), mesenchymaltumors (38.90%), and hematopoietic tumors (4.14%)located in the skin. Among these, 69.25% were benign and30.74% were malignant. The top ten most frequentlydiagnosed cutaneous tumors were epidermal and follicularcysts (12.70%), lipoma (11.36%), mast cell tumors (8.82%),cutaneous histiocytoma (7.49%), basal cell tumors (6.82%),sebaceous gland adenoma (6.68%), sebaceous glandhyperplasia (5.08%), hepatoid gland adenoma (3.61%),apocrine adenocarcinoma (3.07%), and fibroma (2.81%),in order of prevalence. They comprised 68.45% of allcutaneous tumors. These top ten cutaneous tumors weredistributed on the trunk (30.08%), head and neck(20.9%), extremities (19.14%), anal and perianal area(8.59%), and tail (3.91%). The age of the dogs with the tenmost frequent tumors had a mean age of 8.3 years, with arange of 2 months to 19 years. When all types of tumorswere considered together in the entire population, therewas no difference in incidence according to sex.