Open AccessOncogenic Activation of the Wnt/β-Catenin Signaling Pathway in Signet Ring Stromal Cell Tumor of the Ovary
Author(s) -
Janusz Kopczyński,
Artur Kowalik,
Małgorzata Chłopek,
Zeng-Feng Wang,
Stanisław Góźdż,
Jerzy Lasota,
Markku Miettinen
Publication year - 2016
Publication title -
applied immunohistochemistry and molecular morphology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.868
H-Index - 60
eISSN - 1541-2016
pISSN - 1533-4058
DOI - 10.1097/pai.0000000000000271
Subject(s) - wnt signaling pathway , cancer research , stromal cell , ovary , catenin , microbiology and biotechnology , biology , chemistry , signal transduction , genetics
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.