Journal Article

DICER1 RNase IIIb domain mutations are infrequent in testicular germ cell tumours

Stoop, Hans, Eini, Ronak, Gillis, Ad M, Looijenga, Leendert HJ, White, Stefan J, de Boer, Carmela M

2012

Overview

Background Testicular Germ Cell Tumours (TGCT) are the most frequently occurring malignancy in males from 15–45 years of age. They are derived from germ cells unable to undergo physiological maturation, although the genetic basis for this is poorly understood. A recent report showed that mutations in the RNase IIIb domain of DICER1, a micro-RNA (miRNA) processing enzyme, are common in non-epithelial ovarian cancers. DICER1 mutations were found in 60% of Sertoli-Leydig cell tumours, clustering in four codons encoding metal-binding sites. Additional analysis of 14 TGCT DNA samples identified one case that also contained a mutation at one of these sites. Findings A number of previous studies have shown that DICER1 mutations are found in <1% of most cancers. To provide a more accurate estimate of the frequency of such mutations in TGCTs, we have analysed 96 TGCT samples using high resolution melting curve analysis for sequence variants in these four codons. Although we did not detect any mutations in any of these sites, we did identify a novel mutation (c.1725 R>Q) within the RNase IIIb domain in one TGCT sample, which was predicted to disturb DICER1 function. Conclusion Overall our findings suggest a mutation frequency in TGCTs of ~1%. We conclude therefore that hot-spot mutations, frequently seen in Sertoli-Leydig cell tumours, are not common in TGCTs.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amino acids / Analysis / Base Sequence / Binding sites / Biomedical and Life Sciences / Biomedicine / Cancer / Codon / DEAD-box RNA Helicases - genetics / DICER1 / DNA Primers / Gene mutations / Genetic aspects / Genetic testing / Humans / Life Sciences / Male / Medicine/Public Health / MicroRNA / miRNA / Mutation / Mutation detection / Neoplasms, Germ Cell and Embryonal - enzymology / Neoplasms, Germ Cell and Embryonal - genetics / Ovarian cancer / Physiological aspects / Ribonuclease / Ribonuclease III - genetics / RNA processing / Short Report / Technological change / Testicular cancer / Testicular germ cell tumours / Testicular Neoplasms - enzymology / Testicular Neoplasms - genetics / Tumors