Lawrie, C.H. (Charles H.)

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20202

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    Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma
    (2020) Wang, J. (Jun); Fernandez-Mercado, M. (Marta); Goicoechea, I. (Ibai); Larrea, E. (Erika); Guerra-Assunção, J.A. (José Afonso); Ceberio, I. (Izaskun); Enright, A.J. (Anton J.); Fitzgibbon, J. (Jude); Gaafar, A. (Ayman); Lawrie, C.H. (Charles H.); Lobo, C. (Carmen); Okosun, J. (Jessica)
    : the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA).
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    The urinary transcriptome as a source of biomarkers for prostate cancer
    (Cancers, 2020) Urruticoechea, A. (Ander); López, J.I. (José Ignacio); Loizaga-Iriarte, A. (Ana); Goñi, A. (Alai); Goicoechea, I. (Ibai); Roumiguie, M. (Mathieu); Sanz-Jaka, J.P. (Juan Pablo); Solé, C. (Carla); Tellaetxe, M. (Maitena); Vergara, I. (Itziar); Arestin, M. (María); Nogueira, L. (Leonor); Schramm, M. (Maike); Malavaud, B. (Bernard); Carracedo, A. (Arkaitz); Unda, M. (Miguel); Alberdi, A. (Aitor); Armesto, M. (María); Manterola, L. (Lorea); Lawrie, C.H. (Charles H.)
    Prostate cancer (PCa) is the second most common cancer of men and is typically slow-growing and asymptomatic. The use of blood PSA as a screening method has greatly improved PCa diagnosis, but high levels of false positives has raised much interest in alternative biomarkers. We used next-generation sequencing (NGS) to elucidate the urinary transcriptome of whole urine collected from high-stage and low-stage PCa patients as well as from patients with the confounding diagnosis of benign hyperplasia (BPH). We identified and validated five differentially expressed protein-coding genes (FTH1 BRPF1, OSBP, PHC3, and UACA) in an independent validation cohort of small-volume (1 mL) centrifuged urine (n = 94) and non-centrifuged urine (n = 84) by droplet digital (dd)PCR. These biomarkers were able to discriminate between BPH and PCa patients and healthy controls using either centrifuged or non-centrifuged whole urine samples, suggesting that the urinary transcriptome is a valuable source of non-invasive biomarkers for PCa that warrants further investigation.