Oncogenic Activation of the Wnt/β-Catenin Signaling Pathway in Signet Ring Stromal Cell Tumor of the Ovary.
Signet ring stromal cell tumor (SRSCT) of the ovary is a very rare benign ovarian neoplasm. To date, no underlying genetic mechanism has been identified. In this study, 50 oncogenes and tumor suppressor genes were evaluated for mutations in a typical SRSCT using the next-generation DNA sequencing approach. An in-frame deletion of 30 nucleotides in the glycogen serine kinase-3 beta phosphorylation region of the β-catenin gene (CTNNB1) was identified, and the finding was confirmed by Sanger sequencing. This deletion (c.68_97del) at the protein level would lead to a p.Ser23_Ser33delinsThr oncogenic-type mutation. Subsequent immunohistochemistry showed prominent nuclear accumulation of β-catenin and cyclin D1 in tumor cells. Thus, mutational activation of the Wnt/β-catenin pathway could be a crucial event in the molecular pathogenesis of SRSCT of the ovary. These findings may also assist in the diagnosis of this rare tumor.
Departments of *Surgical Pathology †Molecular Diagnostic §Chemotherapy, Holycross Cancer Centre ∥Faculty of Health Sciences, Jan Kochanowski University, Kielce, Poland ‡Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
Janusz
J
Kopczynski
Artur
A
Kowalik
Małgorzata
M
Chłopek
Zeng-Feng
ZF
Wang
Stanisław
S
Góźdź
Jerzy
J
Lasota
Markku
M
Miettinen
D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin