Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry
Kris Ann P Schultz, Anne Harris, Yoav Messinger, Susan Sencer, Shari Baldinger, Louis P Dehner, D Ashley Hill, Kris Ann P Schultz, Anne Harris, Yoav Messinger, Susan Sencer, Shari Baldinger, Louis P Dehner, D Ashley Hill
Abstract
Germline DICER1 mutations have been described in individuals with pleuropulmonary blastoma (PPB), ovarian Sertoli-Leydig cell tumor (SLCT), sarcomas, multinodular goiter, thyroid carcinoma, cystic nephroma and other neoplastic conditions. Early results from the International Ovarian and Testicular Stromal Tumor Registry show germline DICER1 mutations in 48 % of girls and women with SLCT. In this report, a young woman presented with ovarian undifferentiated sarcoma. Four years later, she presented with SLCT. She was successfully treated for both malignancies. Sequence results showed a germline intronic mutation in DICER1. This mutation results in an exact duplication of the six bases at the splice site at the intron 23 and exon 24 junction. Predicted improper splicing leads to inclusion of 10 bases of intronic sequence, frameshift and premature truncation of the protein disrupting the RNase IIIb domain. A second individual with SLCT was found to have an identical germline mutation. In each of the ovarian tumors, an additional somatic mutation in the RNase IIIb domain of DICER1 was found. In rare patients, germline intronic mutations in DICER1 that are predicted to cause incorrect splicing can also contribute to the pathogenesis of SLCT.
Keywords: DICER1; MiRNA; Ovarian cancer; Sarcoma; Sertoli-Leydig cell tumor.
Conflict of interest statement
Conflicts of Interest: The authors each state that he/she has no conflicts of interest to disclose.
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Source: PubMed