title: 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.
  
  
  RESULTS
  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.affiliation: Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Nelly
authors.initials: N
authors.lastname: Sabbaghian
authors.forename: Amin
authors.initials: A
authors.lastname: Bahubeshi
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Shuen
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Marc D
authors.initials: MD
authors.lastname: Tischkowitz
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005091:Exons; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D018239:Seminoma / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013736:Testicular Neoplasms / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
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