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

BMC Research Notes

William D Foulkes³  Katherine L Nathanson⁵  Marc D Tischkowitz²  Peter A Kanetsky⁵  Andrew Y Shuen¹  Amin Bahubeshi⁶  Nelly Sabbaghian⁴ 

[1]Department of Human Genetics, McGill University, Montreal, QC, Canada

[2]Department of Medical Genetics, University of Cambridge, Addenbrooke’s Hospital, Level 6, Addenbrooke’s Treatment Centre Box 134, Cambridge, CB2 0QQ, UK

[3]Research Institute, McGill University Health Centre, Montreal, QC, Canada

[4]Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada

[5]Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

[6]Current Addresses: Faculty of Medicine, University of Toronto, Toronto, ON, Canada

关键词: High-resolution melt analysis;    Mutation analysis;    Dicer;    Germ cell tumors;    microRNA;   

Others  :  1143027
DOI  :  10.1186/1756-0500-6-127

 received in 2012-11-29, accepted in 2013-03-26,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Sabbaghian et al.; licensee BioMed Central Ltd.

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