Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma
de, Kock L
Nature Publishing Group
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Murray, M., Bailey, S., Raby, K., Saini, H., de, K. L., Burke, G., Foulkes, W., et al. (2014). Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis, 3 (e87)https://doi.org/10.1038/oncsis.2014.1
DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic ‘hotspot’ mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G4A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n¼52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P¼0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.
DICER1, microRNA, pleuropulmonary blastoma, serum
We would like to thank the following for providing financial support: SPARKS (NC, MJM), Medical Research Council Fellowship (MJM), TD Bank/LDI scholarship (LdK), Alex’s Lemonade Stand Foundation (WDF), Cancer Research UK (NC) and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 310018 (MT).
European Research Council (310018)
External DOI: https://doi.org/10.1038/oncsis.2014.1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248086
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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