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Murray MJ, Bailey S, Raby KL, et al. Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis. 2014;3:e87doi: 10.1038/oncsis.2014.1.
Murray, M. J., Bailey, S., Raby, K. L., Saini, H. K., de Kock, L., Burke, G. A., Foulkes, W. D., Enright, A. J., Coleman, N., & Tischkowitz, M. (2014). Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis, 3e87. https://doi.org/10.1038/oncsis.2014.1
Murray, M J, et al. "Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma." Oncogenesis vol. 3 (2014): e87. doi: https://doi.org/10.1038/oncsis.2014.1
Murray MJ, Bailey S, Raby KL, Saini HK, de Kock L, Burke GA, Foulkes WD, Enright AJ, Coleman N, Tischkowitz M. Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma. Oncogenesis. 2014 Feb 10;3:e87. doi: 10.1038/oncsis.2014.1. PMID: 24513630; PMCID: PMC3940920.
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Oncogenesis. 2014 Feb 10;3:e87. doi: 10.1038/oncsis.2014.1.

Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma.

Oncogenesis

M J Murray, S Bailey, K L Raby, H K Saini, L de Kock, G A A Burke, W D Foulkes, A J Enright, N Coleman, M Tischkowitz

Affiliations

  1. 1] Department of Paediatric Haematology and Oncology, Addenbrooke's Hospital, Cambridge, UK [2] Department of Pathology, University of Cambridge, Cambridge, UK.
  2. Department of Paediatric Haematology and Oncology, Addenbrooke's Hospital, Cambridge, UK.
  3. Department of Pathology, University of Cambridge, Cambridge, UK.
  4. European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.
  5. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada.
  6. 1] Department of Pathology, University of Cambridge, Cambridge, UK [2] Department of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
  7. Department of Medical Genetics, University of Cambridge, Cambridge, UK.

PMID: 24513630 PMCID: PMC3940920 DOI: 10.1038/oncsis.2014.1

Abstract

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.5425G>A [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 (n=52). 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 (P=0.013). 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.

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