Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours.

Abstract

BACKGROUND:

The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from defects in their processing. As part of a recent study of DICER1 RNase III domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation was identified in a seminoma. To further explore the importance of DICER1 mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ-line DNA samples from 43 probands diagnosed with familial TGCT.

FINDINGS:

We carried out High Resolution Melting Curve Analysis of DICER1 exons 2-12, 14-19, 21 and 24-27. All questionable melt curves were subjected to confirmatory Sanger sequencing.Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon boundaries were included in all analyses. We identified 12 previously reported single nucleotide polymorphisms and two novel single nucleotide variants. No likely deleterious variants were identified; notably no mutations that were predicted to truncate the protein were identified.

CONCLUSIONS:

Taken together with previous studies, the findings reported here suggest a very limited role for either germ-line or somatic DICER1 mutations in the etiology of TGCT.

• Authors: Nelly Sabbaghian, Amin Bahubeshi, Andrew Y Shuen, Peter A Kanetsky, Marc D Tischkowitz, Katherine L Nathanson, William D Foulkes
• Journal: BMC research notes (BMC Res Notes) Vol. 6 Pg. 127 (Apr 01 2013) ISSN: 1756-0500 [Electronic] England
• PMID: 23547758 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• DICER1 protein, human
• Ribonuclease III
• DEAD-box RNA Helicases

Topics

• DEAD-box RNA Helicases (genetics)
• Exons
• Germ-Line Mutation
• Humans
• Male
• MicroRNAs (metabolism)
• Neoplasms, Germ Cell and Embryonal (genetics)
• Polymorphism, Single Nucleotide
• Protein Structure, Tertiary
• Ribonuclease III (genetics, metabolism)
• Seminoma (metabolism)
• Sequence Analysis, DNA
• Testicular Neoplasms (genetics)